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Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia (COMPLEMENT 1)

Primary Purpose

Leukaemia, Lymphocytic, Chronic

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

chlorambucil, tablets

ofatumumab (GSK1841157) infusion

About this trial

This is an interventional treatment trial for Leukaemia, Lymphocytic, Chronic focused on measuring Safety, Untreated, Efficacy, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia (CLL), untreated, Ofatumumab, Oncology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

confirmed CLL diagnosis and active CLL requiring treatment
considered inappropriate for fludarabine-based therapy
not been treated for CLL before
fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
age 18yrs or older
signed written informed consent

Exclusion Criteria:

prior CLL therapy
abnormal/inadequate blood values, liver, and kidney function
certain heart problems, active or chronic infections, serious significant diseases, active autoimmune hemolytic anemia (AIHA) requiring treatment, other current cancer or within last 5 years
CLL transformation
CLL central nervous system involvement
current participation in other clinical study
inability to comply with the protocol activities
lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ofatumumab + chlorambucil

chlorambucil

Arm Description

ofatumumab dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days; chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 treatment cycles

chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)

PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event or death occurred after extensive lost-to-follow-up time or if new anti-cancer therapy was started were censored at the date of the last visit with adequate assessment.

Secondary Outcome Measures

Number of Participants With the Best Overall Response (OR), as Assessed by the IRC

OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM.

Number of Participants Who Were Negative for Minimal Residual Disease (MRD)

MRD was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

Overall Survival

Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the total IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact.

Time to Response, as Assessed by the IRC

Time to response is defined as the time from randomization to the first response (CR, CRi, nPR, or PR). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders. Only responders (CR, CRi, PR, nPR) were included in the analysis.

Duration of Response (DOR), as Assessed by the IRC

DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders.

Time to Progression, as Assessed by the IRC

Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment.

Time to Next Therapy

Time to next therapy is defined as the time from randomization until the start of the next-line of treatment.

Number of Participants With Improvement in ECOG Performance Status of 0 or 1

The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead. Participants with an ECOG performance status of 0 or 1 are shown..

Number of Participants With Improvement in Constitutional Symptoms (CS)

Assessment for the presence of the following symptoms were performed at Screening, Day 1 of each treatment cycle and at every Follow-up visit: night sweats (without signs of infection); unexplained, unintentional weight loss >= 10% within the previous 6 months; recurrent, unexplained fever of greater than 38 degrees celsius or 100.5 degrees fahrenheit for 2 weeks; and extreme fatigue. The best response refers to overall best response in terms of CR, CRi, PR or nPR. Data are presented for constitutional response= yes and no.

Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result

Serum samples for analysis of HAHA were collected at Baseline (Screening), Cycle 4 Day 1 (after 3 months of treatment), and at 1 month and 6 months post last dose of ofatumumab. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive and further evaluated in the titration test to obtain a titer of HAHA.

Cmax and Ctrough of Ofatumumab

Blood samples were collected to assess the plasma concentration of ofatumumab. Maximum concentration (Cmax) and observed drug concentration prior to the next dose (Ctrough) were determined. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of treatment.

Total Plasma Clearance (CL) of Ofatumumab

Plasma clearance is defined as the plasma volume which is totally cleared of drug per unit of time. Blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

AUC(0-tau) of Ofatumumab

Area under the concentration time curve over the dosing interval [AUC(0-tau)] is a measure of drug exposure over time. AUC(0-tau) is defined as the area under the ofatumumab plasma concentration-time curve from dosing to time tau, where tau is the length of the dosing interval of ofatumumab. For estimation of AUC(0-tau), blood samples were collected from participants who received ofatumumab plus chlorambucil at pre-dose and 0.5 hous after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to the ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on duration of treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Volume of Distribution at Steady State (Vss) of Ofatumumab

Volume of distribution at steady state (Vss) is defined as the distribution of a drug between plasma and the rest of the body at steady state. Blood samples were collected from participants who received ofatumumab plus chlorambucil at predose and 0.5 hour after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Plasma Half Life (t1/2) of Ofatumumab

The terminal half-life (t1/2) of ofatumumab is defined as the time required for the plasma concentration of ofatumumab to reach half of its original concentration. Blood samples were collected to assess the plasma half-life of ofatumumab. Blood samples were collected from participants who received ofatumumab plus chlorambucil pre-dose and 0.5 hours after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, pre-dose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, 6, 9 and 12 (Days 29, 57, 113, 141, 225 and 309), depending on the duration of the treatment. Samples were also collected during clinic visits on Day 15 (during Cycle 1) and Day 43 (during Cycle 2) and at 1, 3, and 6 months post-treatment.

Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM)

Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The maximum observed concentration (Cmax) of chlorambucil and PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00].

Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM)

Blood samples for the determination of serum concentrations of chlorambucil and its metabolite PAAM were collected from participants in a substudy on Cycle 3 Day 1. The area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) and over 6 hours (AUC[0-6]) of chlorambucil and AUC(0-6) of PAAM normalized to the administered dose was determined as a measure of exposure and compared to reference data from a prior study (LEUA1001) [No NCT number available for this study; GlaxoSmithKline Document Number RM1998/00449/00].

Change From Baseline in Health Related Quality of Life (HRQOL)

HRQOL was assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLQC30), Chronic Lymphocytic Leukemia module (EORTC QLQ-CLL16), EuorQoL-Five Dimension (EQ-5D), and HCQ. Period (P)1 (Day 85, Day 169, Day 253) and P2 (scheduled follow-up (FU) and withdrawal visits) analysis were considered. Baseline (BL) for P1 was defined as score from screening visit and BL for P2 was defined as the last on-treatment score. The 2 principal QoL outcomes were pre-specified as the Global Health scale (GHS/QOL) of the EORTC QLQ-C30 and fatigue scale of the EORTC QLQ-CLL16. For EORTC QLQ-C30,GHS/Qol, the possible scale range was 0-100 (with 100 being 'best') and a positive difference from BL is indicative of better functioning (range -100 to +100). For the EORTC QLQ-CLL16 fatigue scale, the possible scale range was 0-100 (with 0 being 'best') and a negative difference from BL represents an improvement in fatigue (range -100 to +100).

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher

Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)

Participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented by treatment cycle. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease

AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.

Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study

Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table.

Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM

Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on Cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Full Information

NCT ID

NCT00748189

First Posted

September 5, 2008

Last Updated

June 5, 2019

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00748189

Brief Title

Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia

Acronym

COMPLEMENT 1

Official Title

A Phase III, Open Label, Randomized, Multicenter Trial of Ofatumumab Added to Chlorambucil Versus Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Why Stopped

Majority of patients (62%) had been treated with next line therapies, including new highly effective therapies confounding the interpretation of the OS results.

Study Start Date

December 22, 2008 (Actual)

Primary Completion Date

March 20, 2013 (Actual)

Study Completion Date

May 17, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to chlorambucil in patients with untreated Chronic Lymphocytic Leukemia.

Detailed Description

Chlorambucil, is currently approved for treatment of frontline chronic lymphocytic leukemia, especially, but not limited to the ailing and elderly patient population. Several other more aggressive treatment options are available (e.g. fludarabine), however they are not suitable for all CLL patients, especially the ailing and elderly, due to greater toxicity. Ofatumumab is effective with low toxicity. The addition of ofatumumab to chlorambucil offers potentially a more effective therapy, with limited toxicity. The objective of this study was to evaluate progression-free survival (PFS), overall response and overall survival in subjects with previously untreated CLL with ofatumumab added to chlorambucil versus chlorambucil.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukaemia, Lymphocytic, Chronic

Keywords

Safety, Untreated, Efficacy, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia (CLL), untreated, Ofatumumab, Oncology

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Masking

None (Open Label)

Allocation

Randomized

Enrollment

447 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ofatumumab + chlorambucil

Arm Type

Experimental

Arm Description

Arm Title

chlorambucil

Arm Type

Active Comparator

Arm Description

chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Intervention Type

Drug

Intervention Name(s)

chlorambucil, tablets

Intervention Description

2mg tablets, chlorambucil dose: 10mg/m2 PO at days 1-7 every 28 days; duration: minimum of 3 cycles until best response or maximum of 12 cycles

Intervention Type

Drug

Intervention Name(s)

ofatumumab (GSK1841157) infusion

Other Intervention Name(s)

chlorambucil, tablets

Intervention Description

iv infusion; dose: cycle 1 300mg day 1 and 1000mg day 8, subsequent cycles: 1000mg at day 1 every 28 days;

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS), as Assessed by the Independent Review Committee (IRC)

Description

Time Frame

From randomization to the date of first documented disease progression or death due to any cause, whichever occured first, reported between day of first patient randomized up to about 49 months

Secondary Outcome Measure Information:

Title

Number of Participants With the Best Overall Response (OR), as Assessed by the IRC

Description

Time Frame

From randomization until the 259th PFS event occurred, up to about 49 months

Title

Number of Participants Who Were Negative for Minimal Residual Disease (MRD)

Description

MRD was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

Time Frame

From randomization until the 259th PFS event occurred (Median follow-up approximately 28.9 months)

Title

Overall Survival

Description

Time Frame

From randomization up to about 111 months

Title

Time to Response, as Assessed by the IRC

Description

Time Frame

From randomization uo to about 27 months

Title

Duration of Response (DOR), as Assessed by the IRC

Description

Time Frame

From randomization up to about 43 months

Title

Time to Progression, as Assessed by the IRC

Description

Time Frame

From randomization up to about 49 months

Title

Time to Next Therapy

Description

Time to next therapy is defined as the time from randomization until the start of the next-line of treatment.

Time Frame

From randomization up to about 49 months

Title

Number of Participants With Improvement in ECOG Performance Status of 0 or 1

Description

Time Frame

Baseline, Cycle 3 Day 1, 1 month Follow-up

Title

Number of Participants With Improvement in Constitutional Symptoms (CS)

Description

Time Frame

Baseline, Cycle 3 Day 1, and 1 month Follow-up

Title

Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result

Description

Time Frame

Baseline, Cycle 4 Day 1, 1 Month Follow-up, and 6 Month Follow-up

Title

Cmax and Ctrough of Ofatumumab

Description

Time Frame

Cycle 1 Day 1,Cycle 1 Day 8, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, and Cycle 9 Day 1

Title

Total Plasma Clearance (CL) of Ofatumumab

Description

Time Frame

Cycle 4 Day 1

Title

AUC(0-tau) of Ofatumumab

Description

Time Frame

Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Title

Volume of Distribution at Steady State (Vss) of Ofatumumab

Description

Time Frame

Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 4 Day 1

Title

Plasma Half Life (t1/2) of Ofatumumab

Description

Time Frame

Cycle 4 Day 1

Title

Dose-normalized Cmax of Chlorambucil and Phenylacetic Acid Mustard (PAAM)

Description

Time Frame

Cycle 3 Day 1

Title

Dose-normalized AUC(0-6) and AUC(0-inf) of Chlorambucil and Dose-normalized AUC(0-6) of Phenylacetic Acid Mustard (PAAM)

Description

Time Frame

Cycle 3 Day 1

Title

Change From Baseline in Health Related Quality of Life (HRQOL)

Description

Time Frame

Baseline, Cycle 4 day 1, cycle 7 day 1, 1 month follow-up, 6 month follow-up, 12 month follow-up

Title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Description

Time Frame

From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy, up to approximately 111 months.

Title

Number of Participants With AEs and SAEs of Maximum Severity of Grade 3 or Higher

Description

Time Frame

Title

Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia)

Description

Time Frame

Title

Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease

Description

Time Frame

Title

Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study

Description

Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table.

Time Frame

From start of treatment to the last study visit/withdrawal visit (Median follow-up approximately 28.9 months)

Title

Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM

Description

Time Frame

From start of treatment up to 30 days after last treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: confirmed CLL diagnosis and active CLL requiring treatment considered inappropriate for fludarabine-based therapy not been treated for CLL before fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours age 18yrs or older signed written informed consent Exclusion Criteria: prior CLL therapy abnormal/inadequate blood values, liver, and kidney function certain heart problems, active or chronic infections, serious significant diseases, active autoimmune hemolytic anemia (AIHA) requiring treatment, other current cancer or within last 5 years CLL transformation CLL central nervous system involvement current participation in other clinical study inability to comply with the protocol activities lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Sedona

State/Province

Arizona

ZIP/Postal Code

86336

Country

United States

Facility Name

Novartis Investigative Site

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85704

Country

United States

Facility Name

Novartis Investigative Site

City

Murrieta

State/Province

California

ZIP/Postal Code

92562

Country

United States

Facility Name

Novartis Investigative Site

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80012

Country

United States

Facility Name

Novartis Investigative Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80204

Country

United States

Facility Name

Novartis Investigative Site

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33486

Country

United States

Facility Name

Novartis Investigative Site

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34655

Country

United States

Facility Name

Novartis Investigative Site

City

Ocala

State/Province

Florida

ZIP/Postal Code

34471

Country

United States

Facility Name

Novartis Investigative Site

City

Ocoee

State/Province

Florida

ZIP/Postal Code

34761

Country

United States

Facility Name

Novartis Investigative Site

City

Marietta

State/Province

Georgia

ZIP/Postal Code

30060

Country

United States

Facility Name

Novartis Investigative Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Novartis Investigative Site

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46227

Country

United States

Facility Name

Novartis Investigative Site

City

Lee's Summit

State/Province

Missouri

ZIP/Postal Code

64064

Country

United States

Facility Name

Novartis Investigative Site

City

Raleigh

State/Province

North Carolina

ZIP/Postal Code

27607

Country

United States

Facility Name

Novartis Investigative Site

City

Abilene

State/Province

Texas

ZIP/Postal Code

79606-5208

Country

United States

Facility Name

Novartis Investigative Site

City

Arlington

State/Province

Texas

ZIP/Postal Code

76014

Country

United States

Facility Name

Novartis Investigative Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78731

Country

United States

Facility Name

Novartis Investigative Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

Novartis Investigative Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Novartis Investigative Site

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

Novartis Investigative Site

City

Midland

State/Province

Texas

ZIP/Postal Code

79701

Country

United States

Facility Name

Novartis Investigative Site

City

Odessa

State/Province

Texas

ZIP/Postal Code

79761

Country

United States

Facility Name

Novartis Investigative Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78217

Country

United States

Facility Name

Novartis Investigative Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Novartis Investigative Site

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

Novartis Investigative Site

City

Waco

State/Province

Texas

ZIP/Postal Code

76712

Country

United States

Facility Name

Novartis Investigative Site

City

Webster

State/Province

Texas

ZIP/Postal Code

77598-4420

Country

United States

Facility Name

Novartis Investigative Site

City

Seattle

State/Province

Washington

ZIP/Postal Code

98133

Country

United States

Facility Name

Novartis Investigative Site

City

Vancouver

State/Province

Washington

ZIP/Postal Code

98684

Country

United States

Facility Name

Novartis Investigative Site

City

Yakima

State/Province

Washington

ZIP/Postal Code

98902

Country

United States

Facility Name

Novartis Investigative Site

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Novartis Investigative Site

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Haine-Saint-Paul

ZIP/Postal Code

7100

Country

Belgium

Facility Name

Novartis Investigative Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Porto Alegre

State/Province

Rio De Janeiro

ZIP/Postal Code

91350-200

Country

Brazil

Facility Name

Novartis Investigative Site

City

Sao Paulo

State/Province

São Paulo

ZIP/Postal Code

05403-000

Country

Brazil

Facility Name

Novartis Investigative Site

City

Sao Paulo

State/Province

São Paulo

ZIP/Postal Code

05651-901

Country

Brazil

Facility Name

Novartis Investigative Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Facility Name

Novartis Investigative Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3A1A1

Country

Canada

Facility Name

Novartis Investigative Site

City

Sherbrooke

State/Province

Quebec

ZIP/Postal Code

J1H 5N4

Country

Canada

Facility Name

Novartis Investigative Site

City

Brno

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

Novartis Investigative Site

City

Hradec Kralove

Country

Czechia

Facility Name

Novartis Investigative Site

City

Praha 10

ZIP/Postal Code

100 34

Country

Czechia

Facility Name

Novartis Investigative Site

City

Creteil

ZIP/Postal Code

94010

Country

France

Facility Name

Novartis Investigative Site

City

Pierre Benite

ZIP/Postal Code

69495

Country

France

Facility Name

Novartis Investigative Site

City

Karlsruhe

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

76137

Country

Germany

Facility Name

Novartis Investigative Site

City

Mannheim

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

68161

Country

Germany

Facility Name

Novartis Investigative Site

City

Stuttgart

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

70190

Country

Germany

Facility Name

Novartis Investigative Site

City

Ulm

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

89081

Country

Germany

Facility Name

Novartis Investigative Site

City

Erlangen

State/Province

Bayern

ZIP/Postal Code

91052

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

81241

Country

Germany

Facility Name

Novartis Investigative Site

City

Regensburg

State/Province

Bayern

ZIP/Postal Code

93049

Country

Germany

Facility Name

Novartis Investigative Site

City

Wuerzburg

State/Province

Bayern

ZIP/Postal Code

97070

Country

Germany

Facility Name

Novartis Investigative Site

City

Frankfurt

State/Province

Hessen

ZIP/Postal Code

65929

Country

Germany

Facility Name

Novartis Investigative Site

City

Kassel

State/Province

Hessen

ZIP/Postal Code

34119

Country

Germany

Facility Name

Novartis Investigative Site

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30625

Country

Germany

Facility Name

Novartis Investigative Site

City

Lehrte

State/Province

Niedersachsen

ZIP/Postal Code

31275

Country

Germany

Facility Name

Novartis Investigative Site

City

Essen

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Novartis Investigative Site

City

Koeln

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

50937

Country

Germany

Facility Name

Novartis Investigative Site

City

Moenchengladbach-Rheydt

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

41239

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenster

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

48149

Country

Germany

Facility Name

Novartis Investigative Site

City

Saarbruecken

State/Province

Saarland

ZIP/Postal Code

66113

Country

Germany

Facility Name

Novartis Investigative Site

City

Athens,

ZIP/Postal Code

11 527

Country

Greece

Facility Name

Novartis Investigative Site

City

Thessaloniki

ZIP/Postal Code

564 29

Country

Greece

Facility Name

Novartis Investigative Site

City

Thessaloniki

ZIP/Postal Code

57010

Country

Greece

Facility Name

Novartis Investigative Site

City

Ahmedabad

ZIP/Postal Code

380009

Country

India

Facility Name

Novartis Investigative Site

City

Bangalore

ZIP/Postal Code

560029

Country

India

Facility Name

Novartis Investigative Site

City

Mumbai

ZIP/Postal Code

400012

Country

India

Facility Name

Novartis Investigative Site

City

Mumbai

ZIP/Postal Code

400014

Country

India

Facility Name

Novartis Investigative Site

City

New Delhi

ZIP/Postal Code

110029

Country

India

Facility Name

Novartis Investigative Site

City

Pune

ZIP/Postal Code

411001

Country

India

Facility Name

Novartis Investigative Site

City

Cork

Country

Ireland

Facility Name

Novartis Investigative Site

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

Novartis Investigative Site

City

Galway

Country

Ireland

Facility Name

Novartis Investigative Site

City

James Street

ZIP/Postal Code

Country

Ireland

Facility Name

Novartis Investigative Site

City

Limerick

Country

Ireland

Facility Name

Novartis Investigative Site

City

Tullamore

Country

Ireland

Facility Name

Novartis Investigative Site

City

Waterford

Country

Ireland

Facility Name

Novartis Investigative Site

City

Potenza

State/Province

Basilicata

ZIP/Postal Code

85100

Country

Italy

Facility Name

Novartis Investigative Site

City

Napoli

State/Province

Campania

ZIP/Postal Code

80131

Country

Italy

Facility Name

Novartis Investigative Site

City

Albano Laziale (Roma)

State/Province

Lazio

ZIP/Postal Code

00041

Country

Italy

Facility Name

Novartis Investigative Site

City

Genova

State/Province

Liguria

ZIP/Postal Code

16132

Country

Italy

Facility Name

Novartis Investigative Site

City

Brescia

State/Province

Lombardia

ZIP/Postal Code

25123

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20132

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20133

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20162

Country

Italy

Facility Name

Novartis Investigative Site

City

Ascoli Piceno

State/Province

Marche

ZIP/Postal Code

63100

Country

Italy

Facility Name

Novartis Investigative Site

City

Novara

State/Province

Piemonte

ZIP/Postal Code

28100

Country

Italy

Facility Name

Novartis Investigative Site

City

Bari

State/Province

Puglia

ZIP/Postal Code

70124

Country

Italy

Facility Name

Novartis Investigative Site

City

Palermo

State/Province

Sicilia

ZIP/Postal Code

90146

Country

Italy

Facility Name

Novartis Investigative Site

City

Venezia - Mestre

State/Province

Veneto

ZIP/Postal Code

30174

Country

Italy

Facility Name

Novartis Investigative Site

City

Vicenza

State/Province

Veneto

ZIP/Postal Code

36100

Country

Italy

Facility Name

Novartis Investigative Site

City

Udine

ZIP/Postal Code

33100

Country

Italy

Facility Name

Novartis Investigative Site

City

Amersfoort

ZIP/Postal Code

3818 ES

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Den Haag

ZIP/Postal Code

2545 CH

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Nijmegen

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Rotterdam

ZIP/Postal Code

3015 CE

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Rotterdam

ZIP/Postal Code

3075 EA

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Bialystok

ZIP/Postal Code

15-276

Country

Poland

Facility Name

Novartis Investigative Site

City

Chorzow

ZIP/Postal Code

41-500

Country

Poland

Facility Name

Novartis Investigative Site

City

Lodz

ZIP/Postal Code

93-510

Country

Poland

Facility Name

Novartis Investigative Site

City

Slupsk

ZIP/Postal Code

76-200

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

02-776

Country

Poland

Facility Name

Novartis Investigative Site

City

Wroclaw

ZIP/Postal Code

50-367

Country

Poland

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

125101

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

125167

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Novosibirsk

ZIP/Postal Code

630051

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

St'Petersburg

ZIP/Postal Code

191024

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

St. Petersburg

ZIP/Postal Code

197 089

Country

Russian Federation

Facility Name

Novartis Investigative Site

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

Facility Name

Novartis Investigative Site

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Facility Name

Novartis Investigative Site

City

Hospitalet de Llobregat (Barcelona)

ZIP/Postal Code

08907

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28006

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Novartis Investigative Site

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Novartis Investigative Site

City

Valencia

ZIP/Postal Code

46010

Country

Spain

Facility Name

Novartis Investigative Site

City

Lulea

ZIP/Postal Code

SE-971 80

Country

Sweden

Facility Name

Novartis Investigative Site

City

Stockholm

ZIP/Postal Code

SE-141 86

Country

Sweden

Facility Name

Novartis Investigative Site

City

Uppsala

ZIP/Postal Code

SE-751 85

Country

Sweden

Facility Name

Novartis Investigative Site

City

Plymouth

State/Province

Devon

ZIP/Postal Code

PL6 8DH

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Taunton

State/Province

Somerset

ZIP/Postal Code

TA1 5DA

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Sunderland

State/Province

Tyne

ZIP/Postal Code

SR4 7TP

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Bath

ZIP/Postal Code

BA1 3NG

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Belfast

ZIP/Postal Code

BT9 7AB

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Birmingham

ZIP/Postal Code

B9 5SS

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Bournemouth

ZIP/Postal Code

BH7 7DW

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Bradford

ZIP/Postal Code

BD9 6RJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Canterbury, Kent

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Carshalton

ZIP/Postal Code

SM5 1AA

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Cornwall

ZIP/Postal Code

TR1 3LJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Dudley

ZIP/Postal Code

DY1 2HQ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Exeter

ZIP/Postal Code

EX2 5DW

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Glasgow

ZIP/Postal Code

G12 OYN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Liverpool

ZIP/Postal Code

L7 8XP

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

London

ZIP/Postal Code

EC1M 6BQ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

London

ZIP/Postal Code

SE5 9RS

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Milton Keynes

ZIP/Postal Code

MK6 5LD

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Newcastle-upon-Tyne

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Norwich

ZIP/Postal Code

NR4 7UY

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Oxford

ZIP/Postal Code

OX3 7LJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Peterborough

ZIP/Postal Code

PE3 9GZ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Rhyl, Denbighshire

ZIP/Postal Code

LL18 5UJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Salford

ZIP/Postal Code

M6 8HD

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Stoke on Trent

ZIP/Postal Code

ST4 6QG

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Swindon

ZIP/Postal Code

SN3 6BB

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Uxbridge

ZIP/Postal Code

UB8 3NN

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

IPD Sharing URL

https://www.clinicalstudydatarequest.com

Citations:

PubMed Identifier

33054084

Citation

Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, Yosifov DY, Hillmen P, Offner F, Janssens A, Babu GK, Grosicki S, Mayer J, Panagiotidis P, McKeown A, Gupta IV, Skorupa A, Pallaud C, Bullinger L, Mertens D, Dohner H, Stilgenbauer S. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica. 2020 Oct 1;105(10):2440-2447. doi: 10.3324/haematol.2019.229161.

Results Reference

derived

PubMed Identifier

25882396

Citation

Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9;385(9980):1873-83. doi: 10.1016/S0140-6736(15)60027-7. Epub 2015 Apr 14.

Results Reference

derived

PubMed Identifier

25103870

Citation

Jewell RC, Laubscher K, Lewis E, Fang L, Gafoor Z, Carey J, McKeown A, West S, Wright O, Sedoti D, Dixon I, Hottenstein CS, Chan G. Assessment of the effect of ofatumumab on cardiac repolarization. J Clin Pharmacol. 2015 Jan;55(1):114-21. doi: 10.1002/jcph.376. Epub 2014 Aug 21.

Results Reference

derived

Learn more about this trial

Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia

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Ofatumumab + Chlorambucil vs Chlorambucil Monotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia (COMPLEMENT 1)

Leukaemia, Lymphocytic, Chronic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial