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Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

Primary Purpose

Leukaemia, Lymphocytic, Chronic

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

OFC Infusion

FC infusion

About this trial

This is an interventional treatment trial for Leukaemia, Lymphocytic, Chronic focused on measuring Relapsed, Oncology, Safety, Chronic Lymphocytic Leukemia, Ofatumumab, Efficacy

Eligibility Criteria

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

Key Inclusion Criteria:

confirmed and active CLL requiring treatment
at least one previous treatment for CLL and having achieved a complete or partial remission/response but after a period of 6 or more months, shows evidence of disease progression
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

Key Exclusion Criteria:

diagnosis of refractory CLL (failure to achieve a complete or partial remission/response or disease progression within 6 months of last anti-CLL treatment
abnormal/inadequate blood values, liver and kidney function
certain heart problems, serious significant diseases, AIHA, other current cancers or within the last 5 years
active or chronic infections
use of drugs to suppress allergic or inflammatory responses (glucocorticoids)
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, Fludarabine, Cyclophosphamide

Fludarabine, Cyclophosphamide

Arm Description

Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 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 (progressive disease,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 enlargerd 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 (CLL).

Secondary Outcome Measures

Overall Survival (OS)

Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the last 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. Complete Response/remission(CR) all the criteria at least 2 months after last treatment: no lymphadenopathy(Ly) > 1.5 cm/ hepatomegaly/spleenomegaly/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. Incomplete bone marrow recovery(CRi): CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. Partial Remission/response(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. Nodular PR(nPR): persistent nodules BM.

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 enlargerd 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.

Time to Progression, as Assessed by the IRC

Time to progression is defined as the time from the date of randomization to PD. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd 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.

Time to Next Therapy

Time to next therapy is defined as the time from randomization until the start of the next-line of treatment. Data are presented for participants who took anti-cancer therapies and participants in the ITT population.

Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status

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. ECOG performance status are measured at Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1 and Cycle 6 Day1. During follow period, 1 M after study drug therapy, then every 3 month up to 5 year (up to 60 months). Improvement is defined as a decrease from baseline by at least one step on the ECOG performance status scale (yes/no).

Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time

Participants with no B-symptoms (B-Sy) (no night sweat, no weight loss, no fever and no extreme fatigue) and at least one indicated B-sy(night sweats, weight loss, fever or extreme fatigue) were presented at Screening, Cycle 1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and during follow up period at 1 M after study drug therapy, then every 3 M up to 5 year (up to 60 months).

Percentage 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.

Percentage of Participants With the Best OR, as Assessed by the Investigator

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

MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR. MRD analysis was performed for the participants who were suspected of achieving a primary endpoint CR. MDR 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.

Number of Participants Who Were Negative for MRD Assessed by Investigator

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

Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points

Serum samples for analysis of HAHA were collected at Baseline (Screening), after 3 cycles were compelted, after 1 M and 6 M post last dose. 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.

Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)

AIHA is a condition 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 experienced AIHA are presented.

Number of Participants With Drug Related Infections Reported as AEs and SAEs of Maximum Severity of Grade 3 or Higher

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. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression Adverse Events

Participants with at least one Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. 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 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 or blood supportive care product are included.

Mean Level of 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. Blood samples were collected from each participant and IgA, IgG, and IgM were measured at Baseline, and 1M and 6M after last dose during follow up period.

Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+

CD5+ and CD19+ cells were counted by flow cytometry at Screening (Baseline) on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during the treatment period and after last dose of study drug at 1 M and then every three month follow up up to 45 M. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. day 1 if available, otherwise, screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Change From Baseline in Cell Counts, CD5- CD19+

CD5- CD19+ cells were counted by flow cytometry at Screening (baseline) at Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during treatment period and after last dose of study drug at 1 M and then every three month up to 45 M during follow up period. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. Day 1 if available otherwise screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Prognostic and Biological Markers Correlating With Clinical Response

Blood samples were collected for the assessment of the following prognostic markers at BL: immunoglobulin heavy chain variable region(IgVH) homology; Zeta-Chain-Associated Protein Kinase 70(ZAP70), VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]); beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH included 6q-,11q-, +12q, 17p-, 13q-) , ZAP-70 (positive, negative or intermediate), VH3-21 usage (Yes and No), IgVH homology (>98%, 97%-98% and <97%), beta 2 microglobulin (>3500 microgram per liter [µg/L] and <=3500 µg/L). For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=cytogenetics (CY G).

Changes in Patient Reported Outcome (PRO) Measures and Scores for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16)

The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection scale [IS] (4 items) - and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value was obtained at randomization.

Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit

EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (death) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A Negative health status describes health state worse than death.Baseline is the most recent, non-missing value prior to or on the first study drug dose date.

Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score

EORTC QLQ-C30, a self-reported, cancer-specific instrument assessing 15 domains: physical, role, emotional, cognitive and social functioning, pain,fatigue, nausea and vomiting, insomnia, loss of appetite, constipation, diarrhea, and dyspnea, financial difficulties and a global health status/quality of life (QOF). Functional and symptoms scales were measured on four point Likert scale where 1 = not at all and 4 = very much. Pat. assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Clinically meaningful changes or minimally important differences (MIDs)have been previously established for the EORTC QLQ C30, and categorized as 'small' if the mean change in scores is 5-10 points, 'moderate' if 10-20 points, and 'large' if >20points.

Mean of Health Change Questionnaire (HCQ)

The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions.

Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab

Area under the time-concentration curve (AUC) over the dosing interval (AUC[0-tau]) was evaluated. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab

Blood samples were collected to assess the plasma concentration of ofatumumab.Cmax and Ctrough were determined. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

Time of Occurrence of Cmax (Tmax) of Ofatumumab

Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4.

Full Information

NCT ID

NCT00824265

First Posted

January 15, 2009

Last Updated

June 5, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00824265

Brief Title

Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

Official Title

A Phase III, Open Label, Randomized Trial of Ofatumumab Added to Fludarabine-Cyclophosphamide vs. Fludarabine-Cyclophosphamide Combination in Subjects With Relapsed Chronic Lymphocytic Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

March 12, 2009 (Actual)

Primary Completion Date

December 17, 2014 (Actual)

Study Completion Date

October 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of ofatumumab added to fludarabine-cyclophosphamide in patients with relapsed Chronic Lymphocytic Leukemia (CLL).

Detailed Description

Fludarabine is currently approved for treatment of relapsed Chronic Lymphocytic Leukemia. Studies have shown that drugs in combination with fludarabine have shown more effectiveness than fludarabine alone. The addition of ofatumumab to fludarabine-cyclophosphamide combination offers potentially a more effective therapy, without additional toxicity. The objective of this study was to determine the effect of ofatumumab added to fludarabine and cyclophosphamide in patients with Chronic Lymphocytic Leukemia who have responded previously to therapy but later develop progressive disease and require additional therapy.

6. Conditions and Keywords

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

Leukaemia, Lymphocytic, Chronic

Keywords

Relapsed, Oncology, Safety, Chronic Lymphocytic Leukemia, Ofatumumab, Efficacy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

365 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ofatumumab, Fludarabine, Cyclophosphamide

Arm Type

Experimental

Arm Description

Arm Title

Fludarabine, Cyclophosphamide

Arm Type

Active Comparator

Arm Description

Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Intervention Type

Drug

Intervention Name(s)

OFC Infusion

Intervention Description

Intervention Type

Drug

Intervention Name(s)

FC infusion

Intervention Description

Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250mg/m2 Days 1-3 every 28 days for 6 cycles

Primary Outcome Measure Information:

Title

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

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

Time to Response, as Assessed by the IRC

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

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

Description

Time Frame

From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug)

Title

Time to Progression, as Assessed by the IRC

Description

Time Frame

From randomization up to 5 years after the last dose of study drug

Title

Time to Next Therapy

Description

Time Frame

From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug)

Title

Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status

Description

Time Frame

Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day1, follow up (FU) at 1Month (M) after study drug therapy, 3M, then every 3 month up to 5 year (up to 60 months)

Title

Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time

Description

Time Frame

Screening, Cycle1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and During at 1M after study drug therapy, 3M, then every 3 M up to 5 year (up to 60 months)

Title

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

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

Percentage of Participants With the Best OR, as Assessed by the Investigator

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

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

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

Number of Participants Who Were Negative for MRD Assessed by Investigator

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

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

Description

Time Frame

From first dose of study medication to 60 Days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)

Title

Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points

Description

Time Frame

From start of study drug until 60 days after the last dose of study medication

Title

Number of Participants With Autoimmune Hemolytic Anaemia (AIHA)

Description

AIHA is a condition 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 experienced AIHA are presented.

Time Frame

From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE)

Title

Number of Participants With Drug Related Infections Reported as 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 Adverse Events

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 or blood supportive care product are included.

Time Frame

From randomization up to 5 years after last dose of study drug

Title

Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM

Description

Time Frame

Baseline, 1M and 6M follow up

Title

Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+

Description

Time Frame

Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three months up to 45 M during Follow-up Period

Title

Change From Baseline in Cell Counts, CD5- CD19+

Description

Time Frame

Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three month up to 45 M during Follow-up Period

Title

Prognostic and Biological Markers Correlating With Clinical Response

Description

Time Frame

From randomization up to 5 years after last dose of study drug

Title

Description

Time Frame

Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Title

Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit

Description

Time Frame

Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Title

Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score

Description

Time Frame

Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Title

Mean of Health Change Questionnaire (HCQ)

Description

Time Frame

Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month.

Title

Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab

Description

Time Frame

Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6

Title

Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab

Description

Time Frame

Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5

Title

Time of Occurrence of Cmax (Tmax) of Ofatumumab

Description

Time Frame

Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: confirmed and active CLL requiring treatment at least one previous treatment for CLL and having achieved a complete or partial remission/response but after a period of 6 or more months, shows evidence of disease progression 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 Key Exclusion Criteria: diagnosis of refractory CLL (failure to achieve a complete or partial remission/response or disease progression within 6 months of last anti-CLL treatment abnormal/inadequate blood values, liver and kidney function certain heart problems, serious significant diseases, AIHA, other current cancers or within the last 5 years active or chronic infections use of drugs to suppress allergic or inflammatory responses (glucocorticoids) 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

Boca Raton

State/Province

Florida

ZIP/Postal Code

33486

Country

United States

Facility Name

Novartis Investigative Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612-3833

Country

United States

Facility Name

Novartis Investigative Site

City

Clinton

State/Province

Maryland

ZIP/Postal Code

20735

Country

United States

Facility Name

Novartis Investigative Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64128

Country

United States

Facility Name

Novartis Investigative Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

Novartis Investigative Site

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38120

Country

United States

Facility Name

Novartis Investigative Site

City

Brasilia

State/Province

Goiás

ZIP/Postal Code

70390-150

Country

Brazil

Facility Name

Novartis Investigative Site

City

Porto Alegre

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90610000

Country

Brazil

Facility Name

Novartis Investigative Site

City

Sao Paulo

State/Province

São Paulo

ZIP/Postal Code

05403-000

Country

Brazil

Facility Name

Novartis Investigational Site

City

Porto Alegre

ZIP/Postal Code

91350

Country

Brazil

Facility Name

Novartis Investigative Site

City

Rio de Janeiro

ZIP/Postal Code

20211-030

Country

Brazil

Facility Name

Novartis Investigation Site

City

Rio de Janeiro

ZIP/Postal Code

20230-130

Country

Brazil

Facility Name

Novartis Investigative Site

City

Rio de Janeiro

ZIP/Postal Code

21941-913

Country

Brazil

Facility Name

Novartis Investigational Site

City

Sao Paulo

ZIP/Postal Code

03102-002

Country

Brazil

Facility Name

Novartis Investigative Site

City

Pleven

ZIP/Postal Code

5800

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Plovdiv

ZIP/Postal Code

4000

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1233

Country

Bulgaria

Facility Name

Novartis Investigational Site

City

Sofia

ZIP/Postal Code

1407

Country

Bulgaria

Facility Name

Novartis Investigational Site

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Varna

ZIP/Postal Code

9010

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

New Westminster

State/Province

British Columbia

ZIP/Postal Code

V3L 3W4

Country

Canada

Facility Name

Novartis Investigative Site

City

Kitchener

State/Province

Ontario

ZIP/Postal Code

N2G 1G3

Country

Canada

Facility Name

Novartis Investigative Site

City

Newmarket

State/Province

Ontario

ZIP/Postal Code

L3Y 2P9

Country

Canada

Facility Name

Novartis Investigative Site

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H 8L6

Country

Canada

Facility Name

Novartis Investigative Site

City

Greenfield Park

State/Province

Quebec

ZIP/Postal Code

J4V 2H1

Country

Canada

Facility Name

Novartis Investigative Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H1T 2M4

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

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7N 4H4

Country

Canada

Facility Name

Novartis Investigative Site

City

Karlsruhe

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

76137

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

Stuttgart

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

70376

Country

Germany

Facility Name

Novartis Investigative Site

City

Villingen-Schwenningen

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

78052

Country

Germany

Facility Name

Novartis Investigative Site

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

81241

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

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

Dresden

State/Province

Sachsen

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novartis Investigational Site

City

Hamburg

ZIP/Postal Code

22767

Country

Germany

Facility Name

Novartis Investigational Site

City

Lubeck

ZIP/Postal Code

23562

Country

Germany

Facility Name

Novartis Investigative Site

City

Athens,

ZIP/Postal Code

11 527

Country

Greece

Facility Name

Novartis Investigative Site

City

Athens

ZIP/Postal Code

11527

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

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

Vadodara

ZIP/Postal Code

390007

Country

India

Facility Name

Novartis Investigative Site

City

Potenza

State/Province

Basilicata

ZIP/Postal Code

85100

Country

Italy

Facility Name

Novartis Investigative Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00041

Country

Italy

Facility Name

Novartis Investigative Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00161

Country

Italy

Facility Name

Novartis Investigative Site

City

Genova

State/Province

Liguria

ZIP/Postal Code

16132

Country

Italy

Facility Name

Novartis Investigative Site

City

Pavia

State/Province

Lombardia

ZIP/Postal Code

27100

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

Alessandria

State/Province

Piemonte

ZIP/Postal Code

15100

Country

Italy

Facility Name

Novartis Investigative Site

City

Novara

State/Province

Piemonte

ZIP/Postal Code

28100

Country

Italy

Facility Name

Novartis Investigative Site

City

Catania

State/Province

Sicilia

ZIP/Postal Code

95124

Country

Italy

Facility Name

Novartis Investigative Site

City

Palermo

State/Province

Sicilia

ZIP/Postal Code

90146

Country

Italy

Facility Name

Novartis Investigative Site

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44280

Country

Mexico

Facility Name

Novartis Investigative Site

City

Monterrey

State/Province

Nuevo León

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Novartis Investigative Site

City

Monterrey

State/Province

Nuevo León

ZIP/Postal Code

64710

Country

Mexico

Facility Name

Novartis Investigative Site

City

Mexico City

ZIP/Postal Code

CP 14080

Country

Mexico

Facility Name

Novartis Investigative Site

City

Amersfoort

ZIP/Postal Code

3818 ES

Country

Netherlands

Facility Name

Novartis Investigative Site

City

Den Haag

ZIP/Postal Code

2545 CH

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

Krakow

ZIP/Postal Code

31-501

Country

Poland

Facility Name

Novartis Investigative Site

City

Lodz

ZIP/Postal Code

93-510

Country

Poland

Facility Name

Novartis Investigative Site

City

Opole

ZIP/Postal Code

45-372

Country

Poland

Facility Name

Novartis Investigative Site

City

Slupsk

ZIP/Postal Code

76-200

Country

Poland

Facility Name

Novartis Investigative Site

City

Szczecin

ZIP/Postal Code

71-242

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

02-507

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

02-776

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

02-781

Country

Poland

Facility Name

Novartis Investigative Site

City

Wroclaw

ZIP/Postal Code

50-367

Country

Poland

Facility Name

Novartis Investigative Site

City

Bucharest

ZIP/Postal Code

022328

Country

Romania

Facility Name

Novartis Investigative Site

City

Bucharest

ZIP/Postal Code

050098

Country

Romania

City

Iasi

ZIP/Postal Code

300328

Country

Romania

Facility Name

Novartis Investigative Site

City

Iasi

ZIP/Postal Code

700483

Country

Romania

Facility Name

Novartis Investigative Site

City

Kazan

ZIP/Postal Code

420029

Country

Russian Federation

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

630087

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

Barcelona

ZIP/Postal Code

08916

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

28040

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

Sevilla

ZIP/Postal Code

41014

Country

Spain

Facility Name

Novartis Investigative Site

City

Taichung

ZIP/Postal Code

404

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taipei city

ZIP/Postal Code

100

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Taipei

ZIP/Postal Code

112

Country

Taiwan

Facility Name

Novartis Investigational Site

City

Taipei

ZIP/Postal Code

404

Country

Taiwan

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10400

Country

Thailand

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Novartis Investigative Site

City

Cherkasy

ZIP/Postal Code

18009

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Dnipropetrovsk

ZIP/Postal Code

49102

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Kharkiv

ZIP/Postal Code

61070

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Khmelnytskyi

ZIP/Postal Code

29000

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Kyiv

ZIP/Postal Code

03022

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Kyiv

ZIP/Postal Code

04112

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Lviv

ZIP/Postal Code

79044

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Makiivka

ZIP/Postal Code

86132

Country

Ukraine

Facility Name

Novartis Investigational Site

City

Simferopil

ZIP/Postal Code

95023

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Vinnitsa

ZIP/Postal Code

21018

Country

Ukraine

Facility Name

Novartis Investigational Site

City

Zhytomyr

ZIP/Postal Code

10002

Country

Ukraine

Facility Name

Novartis Investigative Site

City

Birmingham

ZIP/Postal Code

B9 5SS

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Bradford

ZIP/Postal Code

BD96RJ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Burton on Trent

ZIP/Postal Code

DE13 0RB

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Cottingham

ZIP/Postal Code

HU16 5JQ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Dudley

ZIP/Postal Code

DY1 2HQ

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Glasgow

ZIP/Postal Code

G12 OYN

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Leicester

ZIP/Postal Code

LE1 5WW

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

Sutton

ZIP/Postal Code

SM5 1AA

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Swindon

ZIP/Postal Code

SN3 6BB

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Truro

ZIP/Postal Code

TR1 3LJ

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

Undecided

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

Citations:

PubMed Identifier

27830957

Citation

Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, Loscertales J, Kryachok I, Kloczko J, Rekhtman G, Homenda W, Blonski JZ, McKeown A, Chang CN, Bal V, Lisby S, Gupta IV, Grosicki S. Health-related quality of life and patient-reported outcomes of ofatumumab plus fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide in the COMPLEMENT 2 trial of patients with relapsed CLL. Leuk Lymphoma. 2017 Jul;58(7):1598-1606. doi: 10.1080/10428194.2016.1253837. Epub 2016 Nov 10.

Results Reference

derived

PubMed Identifier

27731748

Citation

Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, Loscertales J, Kryachok I, Kloczko J, Rekhtman G, Homenda W, Blonski JZ, McKeown A, Gorczyca MM, Carey JL, Chang CN, Lisby S, Gupta IV, Grosicki S. Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial. Leuk Lymphoma. 2017 May;58(5):1084-1093. doi: 10.1080/10428194.2016.1233536. Epub 2016 Oct 12.

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 Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

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Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

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