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

Lymphoma, Follicular Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00562965
• Other study ID #: 3129K4-3301
• Secondary ID: B19310062007-000
• Status: Terminated
• Phase: Phase 3
• First received: November 21, 2007
• Last updated: December 8, 2017
• Start date: November 2007
• Est. completion date: April 2011

Study information

• Verified date: December 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

Country	Name	City	State
Argentina	Centro de Transplantes de medula Osea de Rosario, CETRAMOR	Rosario	Santa FE
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Oncologisch Centrum GZA - Location St. Augustinus	Wilrijk
Canada	Hopital Charles LeMoyne	Greenfield Park	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	C.H.A. Enfant-Jesus	Quebec
Canada	CHUS-Hopital Fleurimont	Sherbrooke	Quebec
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin	NEW Territories
India	B. P. Poddar Hospital and Medical Research Ltd.	Kolkata	WEST Bengal
India	Jehangir Clinical Development Centre	Pune	Maharashtra
India	MMF Joshi Hospital and Ratna Memorial Hospital	Pune	Maharashtra
Italy	Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo	Pavia
Korea, Republic of	Yonsei University Health System-Severance Hospital	Seoul
Mexico	Hospital Universitario de Nuevo Leon	Monterrey	Nuevo LEON
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Portugal	Hospitais Da Universidade De Coimbra	Coimbra
Russian Federation	Moscow Regional Research Clinical Institute named after Vladimirsky	Moscow
South Africa	Wits Donald Gordon Clinical Trial Site	Johannesburg	Gauteng
Spain	Hospital Santa Creu I Sant Pau	Barcelona
Spain	Hospital de La Princesa	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
United States	Advanced Oncology Associates	Armonk	New York
United States	The Harry & Jeanette Weinberg Cancer Inst at Franklin Square	Baltimore	Maryland
United States	Avi Einzing, MD	Bronx	New York
United States	Hematology and Oncology Associates	Columbus	Mississippi
United States	Hematology and Oncology Associates	Corinth	Mississippi
United States	Deaconess Clinic	Evansville	Indiana
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Facey Medical Group	Mission Hills	California
United States	Hematology Oncology Associates of Northern New Jersy	Morristown	New Jersey
United States	Advanced Oncology Associates	New Rochelle	New York
United States	Newland Medical Associates	Novi	Michigan
United States	Marc Zimmerman, MD	Pomona	New York
United States	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	Newland Medical Associates, PC	Southfield	Michigan
United States	Hematology and Oncology Associates at Bridgepoint	Tupelo	Mississippi
United States	Wenatchee Valley Medical Center	Wenatchee	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	UCB Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Canada,  Hong Kong,  India,  Italy,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Russian Federation,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings	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.	Baseline up to 42 days post-treatment
Other	Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs)	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.	Baseline up to 42 days post-treatment
Other	Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings	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]).	Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)
Other	Number of Participants With Clinically Significant Change From Baseline in Vital Signs	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).	Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)
Primary	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.	Baseline until disease progression or death or up to 1 year after last dose of study drug
Secondary	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).	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
Secondary	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.	Baseline up to Month 6, 12, 24
Secondary	Pharmacokinetics of Inotuzumab Ozogamicin in Combination With Rituximab		0, 1, 168 hours on Cycle 1, 2; 0, 1, 2, 168 hours on Cycle 3, 4

External Links

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