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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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ClinicalTrials.gov Identifier: NCT00562965
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : November 26, 2007
Results First Posted : January 9, 2018
Last Update Posted : January 9, 2018
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Lymphoma, Follicular Drug: inotuzumab ozogamicin Drug: rituximab Drug: cyclophosphamide Drug: vincristine Drug: prednisone/prednisolone Drug: mitoxantrone Drug: fludarabine Drug: dexamethasone Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
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
Actual Study Start Date : November 2007
Primary Completion Date : April 2011
Study Completion Date : April 2011


Arm Intervention/treatment
Experimental: A
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.
Drug: inotuzumab ozogamicin
IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.
Drug: rituximab
IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
Active Comparator: B
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.
Drug: rituximab
intravenous rituximab at a dose of 375 mg/m2 on day 1
Drug: cyclophosphamide
intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1
Drug: vincristine
intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1
Drug: prednisone/prednisolone
oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5
Drug: mitoxantrone
mitoxantrone 10 mg/m2 intravenous on day 2
Drug: fludarabine
fludarabine 25 mg/m2 intravenous on days 2 through 4
Drug: dexamethasone
oral dexamethasone 20 mg/day on days 1-5



Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Baseline until disease progression or death or up to 1 year after last dose of study drug ]
    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 :
  1. Percentage of Participants With Objective Response (OR) [ 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 ]
    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).

  2. Overall Survival Probability at Months 6, 12 and 24 [ Time Frame: Baseline up to Month 6, 12, 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.

  3. 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 Outcome Measures:
  1. Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings [ Time Frame: Baseline up to 42 days post-treatment ]
    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.

  2. Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 42 days post-treatment ]
    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.

  3. Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings [ 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) ]
    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]).

  4. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ 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) ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00562965


  Show 39 Study Locations
Sponsors and Collaborators
Pfizer
UCB Pharma
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00562965     History of Changes
Other Study ID Numbers: 3129K4-3301
B1931006 ( Other Identifier: Alias Study Number )
2007-000219-27 ( EudraCT Number )
First Posted: November 26, 2007    Key Record Dates
Results First Posted: January 9, 2018
Last Update Posted: January 9, 2018
Last Verified: December 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Prednisolone acetate
Methylprednisolone acetate
Dexamethasone
Prednisone
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone hemisuccinate
Prednisolone phosphate
Fludarabine
Fludarabine phosphate
Cyclophosphamide
Rituximab
Vincristine
Mitoxantrone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents