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

NCT00562965 | Terminated Phase 3 Results DMC

• 3 other identifiers: 3129K4-3301B19310062007-000219-27
• Study Type: interventional
• Target: 29
• Locations: 14 countries
• Sites: 39

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.

Conditions

Lymphoma, Follicular

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percentage of Participants With Objective Response (OR)

  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

• Overall Survival Probability at Months 6, 12 and 24

  Baseline up to Month 6, 12, 24

• 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

Other Outcomes (4)

• Number of Participants With Clinically Significant Change From Baseline in QT Interval Findings

  Baseline up to 42 days post-treatment

• Number of Participants With Grade 3 or 4 Treatment Emergent Adverse Events (TEAEs)

  Baseline up to 42 days post-treatment

• Number of Participants With Clinically Significant Change From Baseline in Laboratory Findings

  Baseline up to 42 days post-treatment, disease follow up (every 12 weeks for a minimum of 1 year and up to 2 years)

Study Arms (2)

A

EXPERIMENTAL

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; Drug: rituximab

B

ACTIVE COMPARATOR

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; Drug: cyclophosphamide; Drug: vincristine; Drug: prednisone/prednisolone; Drug: mitoxantrone; Drug: fludarabine; Drug: dexamethasone

Interventions

inotuzumab ozogamicin DRUG

IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.

A

rituximab DRUG

IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.

A

cyclophosphamide DRUG

intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1

B

vincristine DRUG

intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1

B

prednisone/prednisolone DRUG

oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5

B

mitoxantrone DRUG

mitoxantrone 10 mg/m2 intravenous on day 2

B

fludarabine DRUG

fludarabine 25 mg/m2 intravenous on days 2 through 4

B

dexamethasone DRUG

oral dexamethasone 20 mg/day on days 1-5

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• UCB Pharma: collaborator

Study Sites (39)

Facey Medical Group

Mission Hills, California, 91345, United States

Location

Deaconess Clinic

Evansville, Indiana, 47713, United States

Location

The Harry & Jeanette Weinberg Cancer Inst at Franklin Square

Baltimore, Maryland, 21237, United States

Location

Newland Medical Associates

Novi, Michigan, 48374, United States

Location

Newland Medical Associates, PC

Southfield, Michigan, 48075, United States

Location

Park Nicollet Frauenshuh Cancer Center

Saint Louis Park, Minnesota, 55426, United States

Location

Hematology and Oncology Associates

Columbus, Mississippi, 39706, United States

Location

Hematology and Oncology Associates

Corinth, Mississippi, 38834, United States

Location

Hematology and Oncology Associates at Bridgepoint

Tupelo, Mississippi, 38801, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Hematology Oncology Associates of Northern New Jersy

Morristown, New Jersey, 07960, United States

Location

Advanced Oncology Associates

Armonk, New York, 10504, United States

Location

Advanced Oncology Associates

New Rochelle, New York, 10801, United States

Location

Marc Zimmerman, MD

Pomona, New York, 10970, United States

Location

Avi Einzing, MD

The Bronx, New York, 10461, United States

Location

Wenatchee Valley Medical Center

Wenatchee, Washington, 98801, United States

Location

Centro de Transplantes de medula Osea de Rosario, CETRAMOR

Rosario, Santa Fe Province, S2000AYW, Argentina

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Oncologisch Centrum GZA - Location St. Augustinus

Wilrijk, 2610, Belgium

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

C.H.A. Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Prince of Wales Hospital

Shatin, NEW Territories, Hong Kong

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Jehangir Clinical Development Centre

Pune, Maharashtra, 411001, India

Location

MMF Joshi Hospital and Ratna Memorial Hospital

Pune, Maharashtra, 411004, India

Location

B. P. Poddar Hospital and Medical Research Ltd.

Kolkata, West Bengal, 700053, India

Location

Divisione di Ematologia - Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Hospital Universitario de Nuevo Leon

Monterrey, Nuevo León, 64460, Mexico

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Hospitais Da Universidade De Coimbra

Coimbra, 3000-075, Portugal

Location

Moscow Regional Research Clinical Institute named after Vladimirsky

Moscow, 120110, Russia

Location

Wits Donald Gordon Clinical Trial Site

Johannesburg, Gauteng, 2193, South Africa

Location

Yonsei University Health System-Severance Hospital

Seoul, 120-752, South Korea

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital de La Princesa

Madrid, 28006, Spain

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Inotuzumab Ozogamicin; Rituximab; Cyclophosphamide; Vincristine; Prednisone; Prednisolone; Mitoxantrone; fludarabine; Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Quinones; Steroids, Fluorinated

Limitations and Caveats

Study did not met estimated enrollment of approximately 978 participants,thus analysis and conclusions were limited by small number of enrolled participants.Termination was not prompted by identification of safety concerns with inotuzumab ozogamicin.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2007
• First Posted: November 26, 2007
• Study Start: November 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: January 9, 2018
• Results First Posted: January 9, 2018

Record last verified: 2017-12

Locations

KR (1); ES (3); ME (1); AR (1); IN (3); PT (1); BE (2); IT (1); PL (1); HK (2); ZA (1); US (17); RU (1); CA (4)