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Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)

Primary Purpose

Lymphoma, Follicular

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
inotuzumab ozogamicin
rituximab
rituximab
cyclophosphamide
vincristine
prednisone/prednisolone
mitoxantrone
fludarabine
dexamethasone
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Lymphoma, Follicular

Eligibility Criteria

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

Inclusion Criteria:

  • Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).
  • Age 18 years or older.
  • ECOG performance status <= 2.
  • ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.
  • At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.

Exclusion Criteria:

  • Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
  • Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.

Sites / Locations

  • Facey Medical Group
  • Deaconess Clinic
  • The Harry & Jeanette Weinberg Cancer Inst at Franklin Square
  • Newland Medical Associates
  • Newland Medical Associates, PC
  • Park Nicollet Frauenshuh Cancer Center
  • Hematology and Oncology Associates
  • Hematology and Oncology Associates
  • Hematology and Oncology Associates at Bridgepoint
  • Hackensack University Medical Center
  • The Cancer Center at Hackensack University Medical Center
  • Hematology Oncology Associates of Northern New Jersy
  • Advanced Oncology Associates
  • Avi Einzing, MD
  • Advanced Oncology Associates
  • Marc Zimmerman, MD
  • Wenatchee Valley Medical Center
  • Centro de Transplantes de medula Osea de Rosario, CETRAMOR
  • Universitair Ziekenhuis Gent
  • Oncologisch Centrum GZA - Location St. Augustinus
  • Hopital Charles LeMoyne
  • Jewish General Hospital
  • CHUS-Hopital Fleurimont
  • C.H.A. Enfant-Jesus
  • Prince of Wales Hospital
  • Queen Mary Hospital
  • Jehangir Clinical Development Centre
  • MMF Joshi Hospital and Ratna Memorial Hospital
  • B. P. Poddar Hospital and Medical Research Ltd.
  • Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo
  • Yonsei University Health System-Severance Hospital
  • Hospital Universitario de Nuevo Leon
  • Instytut Hematologii i Transfuzjologii
  • Hospitais Da Universidade De Coimbra
  • Moscow Regional Research Clinical Institute named after Vladimirsky
  • Wits Donald Gordon Clinical Trial Site
  • Hospital Universitario Puerta de Hierro
  • Hospital Santa Creu I Sant Pau
  • Hospital de La Princesa

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

A

B

Arm Description

Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days.

Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)
PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.

Secondary Outcome Measures

Percentage of Participants With Objective Response (OR)
OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size [at least 1.5 centimeter(cm) or less],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).
Overall Survival Probability at Months 6, 12 and 24
Overall survival was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.
Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab

Full Information

First Posted
November 21, 2007
Last Updated
December 8, 2017
Sponsor
Pfizer
Collaborators
UCB Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT00562965
Brief Title
Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)
Official Title
An Open-label, Randomized, Phase 3 Study Of Inotuzumab Ozogamicin (Cmc-544) Administered In Combination With Rituximab Compared To A Defined Investigator's Choice Therapy In Subjects With Relapsed Or Refractory, Cd22- Positive, Follicular B-cell Non Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
See termination reason in detailed description.
Study Start Date
November 2007 (Actual)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
UCB Pharma

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This protocol is designed to assess the efficacy and safety of inotuzumab ozogamicin given with rituximab compared to a defined investigator's choice therapy. Subjects will be randomized to one of these two arms of the study.
Detailed Description
On January 14th 2009, enrollment in the study was discontinued because of poor enrollment and because it was unlikely that the study would meet the estimated enrollment of approximately 978 subjects. The decision was not prompted by the identification of any safety signals in this or other studies. Active treatment and follow-up of the already enrolled subjects was continued. On July, 22th 2010 , the study was amended to shorten the long-term follow-up to one year after active treatment.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days.
Arm Title
B
Arm Type
Active Comparator
Arm Description
Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5.
Intervention Type
Drug
Intervention Name(s)
inotuzumab ozogamicin
Intervention Description
IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
intravenous rituximab at a dose of 375 mg/m2 on day 1
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Description
intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1
Intervention Type
Drug
Intervention Name(s)
prednisone/prednisolone
Intervention Description
oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5
Intervention Type
Drug
Intervention Name(s)
mitoxantrone
Intervention Description
mitoxantrone 10 mg/m2 intravenous on day 2
Intervention Type
Drug
Intervention Name(s)
fludarabine
Intervention Description
fludarabine 25 mg/m2 intravenous on days 2 through 4
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
oral dexamethasone 20 mg/day on days 1-5
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS was defined as the time from randomization to disease progression or death due to any cause, whichever occurred first, censored at the last tumor evaluation date. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.44.
Time Frame
Baseline until disease progression or death or up to 1 year after last dose of study drug
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Response (OR)
Description
OR was based on assessment of complete response(CR),unconfirmed CR(Cru),partial response(PR) as per International Response Criteria for Non-Hodgkin's Lymphoma.Confirmed response=response persists on repeat imaging at least 4 weeks after initial response.CR=complete disappearance of all detectable clinical/radiographic evidence of disease,lymph nodes regressed to normal size [at least 1.5 centimeter(cm) or less],spleen regressed,not palpable on physical examination,bone marrow infiltrate cleared on repeat aspiration/biopsy.PR=at least 50 percent (%) decrease in sum of product diameters of 6 greatest dominant nodes,no increase in other nodes,liver/spleen,no new sites of disease. CRu=residual lymph node greater than 1.5 cm in transverse diameter that has regressed more than 75% in product diameter.Individual nodes previously confluent,regressed more than 75% in product diameters.Indeterminate bone marrow (increased number/size of lymph aggregates without cytologic/architectural atypia).
Time Frame
Baseline, every 6 to 12 weeks during treatment period, end of treatment (EOT) (42 days after last dose), every 12 weeks during follow-up for up to 1 year after the last dose of study drug
Title
Overall Survival Probability at Months 6, 12 and 24
Description
Overall survival was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. Participants who withdrew or lost to follow-up from study without having death documented were censored at the date of last contact. Kaplan-Meier estimates of the probability of survival at 6, 12 and 24 months was used to estimate the survival function.
Time Frame
Baseline up to Month 6, 12, 24
Title
Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab
Time Frame
0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4
Other Pre-specified Outcome Measures:
Title
Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings
Description
Assessments of QT interval was performed only in rituximab + inotuzumab ozogamicinin group. QT interval corrected using Fridericia's formula (QTcF) and Bazett's formula (QTcB) was analyzed as per common terminology criteria for adverse events (CTCAE) version 3.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening or disabling AE, Grade 5 = death related to AE. Number of participants with change in CTCAE grading at post-baseline time point compared to the baseline were presented. The post-baseline value was defined as the maximum grade after the first dose date on or before the end of treatment.
Time Frame
Baseline up to 42 days post-treatment
Title
Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs)
Description
AE=any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Grade 3 (Severe) events=unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment. Grade 4 (Life-threatening) events caused participant to be in imminent danger of death. TEAE=between first dose of study drug and up to 42 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame
Baseline up to 42 days post-treatment
Title
Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings
Description
Criteria for laboratory test abnormality: Blood Chemistry (alkaline phosphatase [greater than{>}5*upper limit of normal {ULN}, calcium [less than {<}1.75 millimole per liter {mmol/L}, creatinine [>3*ULN], glucose [>13.9 mmol/L], phosphorous [<0.6 mmol/L], potassium [<3 mmol/L], aspartate transaminase [>5.0*ULN], total bilirubin [>3*ULN]), Coagulation (international normalized ratio [>2*ULN]), Hematology (hemoglobin [<80 grams/Liter], lymphocytes [<0.5*10^9/L], absolute neutrophil count [<1*10^9/L], platelet count [<50*10^9/L], WBC [<2.0*10^9/L]).
Time Frame
Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)
Title
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description
Criteria for determining significant change from baseline in vital signs abnormalities: heart rate value of <40 beats per minute and value >150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, temperature <32 or >40 degree centigrade, and body weight>=10% increase or decrease of body weight in kilogram (kg).
Time Frame
Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination). Age 18 years or older. ECOG performance status <= 2. ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN. At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated. Exclusion Criteria: Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma. Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Facey Medical Group
City
Mission Hills
State/Province
California
ZIP/Postal Code
91345
Country
United States
Facility Name
Deaconess Clinic
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
The Harry & Jeanette Weinberg Cancer Inst at Franklin Square
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
Newland Medical Associates
City
Novi
State/Province
Michigan
ZIP/Postal Code
48374
Country
United States
Facility Name
Newland Medical Associates, PC
City
Southfield
State/Province
Michigan
ZIP/Postal Code
48075
Country
United States
Facility Name
Park Nicollet Frauenshuh Cancer Center
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55426
Country
United States
Facility Name
Hematology and Oncology Associates
City
Columbus
State/Province
Mississippi
ZIP/Postal Code
39706
Country
United States
Facility Name
Hematology and Oncology Associates
City
Corinth
State/Province
Mississippi
ZIP/Postal Code
38834
Country
United States
Facility Name
Hematology and Oncology Associates at Bridgepoint
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
The Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Hematology Oncology Associates of Northern New Jersy
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Advanced Oncology Associates
City
Armonk
State/Province
New York
ZIP/Postal Code
10504
Country
United States
Facility Name
Avi Einzing, MD
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Advanced Oncology Associates
City
New Rochelle
State/Province
New York
ZIP/Postal Code
10801
Country
United States
Facility Name
Marc Zimmerman, MD
City
Pomona
State/Province
New York
ZIP/Postal Code
10970
Country
United States
Facility Name
Wenatchee Valley Medical Center
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States
Facility Name
Centro de Transplantes de medula Osea de Rosario, CETRAMOR
City
Rosario
State/Province
Santa FE
ZIP/Postal Code
S2000AYW
Country
Argentina
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Oncologisch Centrum GZA - Location St. Augustinus
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Hopital Charles LeMoyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
CHUS-Hopital Fleurimont
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
C.H.A. Enfant-Jesus
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Prince of Wales Hospital
City
Shatin
State/Province
NEW Territories
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Jehangir Clinical Development Centre
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
MMF Joshi Hospital and Ratna Memorial Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
Facility Name
B. P. Poddar Hospital and Medical Research Ltd.
City
Kolkata
State/Province
WEST Bengal
ZIP/Postal Code
700053
Country
India
Facility Name
Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Yonsei University Health System-Severance Hospital
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Hospital Universitario de Nuevo Leon
City
Monterrey
State/Province
Nuevo LEON
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Hospitais Da Universidade De Coimbra
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Moscow Regional Research Clinical Institute named after Vladimirsky
City
Moscow
ZIP/Postal Code
120110
Country
Russian Federation
Facility Name
Wits Donald Gordon Clinical Trial Site
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
Facility Name
Hospital Universitario Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Santa Creu I Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital de La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain

12. IPD Sharing Statement

Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=3129K4-3301&StudyName=Study%20Comparing%20Inotuzumab%20Ozogamicin%20In%20Combination%20With%20Rituximab%20Versus%20Defined%20Investigator%27s%20Choice%20In%20Follicular%20Non-Hodgkin%27s%20Lymp
Description
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Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)

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