A Study of Pinatuzumab Vedotin (DCDT2980S) Combined With Rituximab or Polatuzumab Vedotin (DCDS4501A) Combined With Rituximab or Obinutuzumab in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL)

NCT ID: NCT01691898

Last Updated: 2020-02-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

231 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-27

Study Completion Date

2019-02-07

Brief Summary

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This multicenter, open-label study will evaluate the safety and efficacy of pinatuzumab vedotin (DCDT2980S) or polatuzumab vedotin (DCDS4501A) in combination with rituximab (RTX), as well as of polatuzumab vedotin in combination with obinutuzumab in participants with relapsed or refractory (r/r) follicular lymphoma (FL) and r/r diffuse large B-cell lymphoma (DLBCL).

Detailed Description

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Conditions

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Follicular Lymphoma Diffuse Large B-Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A (FL+DLBCL): RTX+Pinatuzumab,Then RTX+Polatuzumab

For the first 2 cycles, RTX 375 milligrams per square meter (mg/m\^2) will be given by intravenous (IV) infusion on Day 1 and pinatuzumab vedotin 2.4 milligrams per kilogram (mg/kg) will be administered by IV infusion on Day 2 to Arm A participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and pinatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop disease progression (PD) will be further treated with RTX 375 mg/m\^2 followed by polatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).

Group Type EXPERIMENTAL

Pinatuzumab Vedotin

Intervention Type DRUG

Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Rituximab

Intervention Type DRUG

RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.

Arm B (FL+DLBCL): RTX+Polatuzumab,Then RTX+Pinatuzumab

For the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 2.4 mg/kg will be administered by IV infusion on Day 2 to Arm B participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle. Participants who develop PD would be further treated with RTX 375 mg/m\^2 followed by pinatuzumab vedotin 2.4 mg/kg IV infusion on Day 1, beginning no later than 42 days after the last dose of the prior study treatment until a second PD event relative to the tumor assessment, documenting PD on the initial study treatment, clinical deterioration, and/or intolerance to the crossover treatment for up to a maximum of 1 year (17 cycles on an every-21-day schedule).

Group Type EXPERIMENTAL

Pinatuzumab Vedotin

Intervention Type DRUG

Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Rituximab

Intervention Type DRUG

RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.

Cohort C (FL): RTX + Polatuzumab

For the first 2 cycles, RTX 375 mg/m\^2 will be given by IV infusion on Day 1 and polatuzumab vedotin 1.8 mg/kg will be administered by IV infusion on Day 2 to Cohort C participants (with r/r FL). In the absence of any infusion-related adverse events, RTX and polatuzumab may be administered on the same day (Day 1) in subsequent cycles beginning with the third cycle for up to a maximum of 1 year (17 cycles on an every-21-day schedule) or significant toxicity, PD, or withdrawal from study.

Group Type EXPERIMENTAL

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Rituximab

Intervention Type DRUG

RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.

Cohort E (FL+DLBCL): Obinutuzumab + Polatuzumab

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort E participants (with r/r FL and DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Cohort G (Expansion, FL): Obinutuzumab + Polatuzumab

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort G participants (with r/r FL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort G participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Cohort H (Expansion, DLBCL): Obinutuzumab + Polatuzumab

For the first cycle, obinutuzumab will be given by IV infusion on Days 1, 8, and 15. Polatuzumab vedotin 1.8 mg/kg IV infusion will be given on Day 2 of the first cycle to Cohort H participants (with r/r DLBCL). In the absence of any infusion-related adverse events, obinutuzumab and polatuzumab vedotin may be administered on the same day (Day 1) in subsequent cycles beginning with the second cycle of the dose-expansion period to cohort H participants up to a maximum of 8 cycles or significant toxicity, PD, or withdrawal from study.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

Polatuzumab Vedotin

Intervention Type DRUG

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Interventions

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Obinutuzumab

Obinutuzumab 1000 mg will be administered by IV infusion on Days 1, 8, 15 of first 21-Day cycle and on Day 1 of subsequent 21-day cycles for up to 8 cycles.

Intervention Type DRUG

Pinatuzumab Vedotin

Pinatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Intervention Type DRUG

Polatuzumab Vedotin

Polatuzumab Vedotin 1.8 or 2.4 mg/kg administered by IV infusion on Day 1 or 2 of every 21-day cycle.

Intervention Type DRUG

Rituximab

RTX 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle.

Intervention Type DRUG

Other Intervention Names

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GA101, Gazyva, Gazyvaro DCDT2980S DCDS4501A MabThera/Rituxan

Eligibility Criteria

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Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Life expectancy of at least 12 weeks
* History of histologically documented r/r Grades 1 to 3a FL, or r/r DLBCL
* Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment
* Have a clinical indication for treatment as determined by the investigator
* Must have at least one bi-dimensionally measurable lesion (greater than \[\>\] 1.5 centimeters \[cm\] in its largest dimension by CT scan or Magnetic Resonance Imaging \[MRI\])

Exclusion Criteria

* Prior use of any monoclonal antibody, radio-immuno-conjugate or antibody drug conjugate within 4 weeks before study start
* Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start
* Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade less than equal to (\</=) 2 prior study start
* Completion of autologous stem cell transplant (SCT) within 100 days prior study start
* Prior allogeneic SCT
* Eligibility for autologous SCT (participants with r/r DLBCL)
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
* History of other malignancy that could affect compliance with the protocol or interpretation of results
* Current or past history of central nervous system lymphoma
* Current Grade \>1 peripheral neuropathy
* Vaccination with a live vaccine within 28 days prior to treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, United States

Site Status

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Site Status

Florida Cancer Specialists - Fort Myers (Colonial Center Dr)

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists; Sarasota

Sarasota, Florida, United States

Site Status

Univ of Michigan Med School; Hematology Oncology

Ann Arbor, Michigan, United States

Site Status

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, United States

Site Status

Hematology Oncology Associates; Carol G. Simon Ctr

Morristown, New Jersey, United States

Site Status

Regional Cancer Care Associates LLC - Morristown

Morristown, New Jersey, United States

Site Status

Roswell Park Cancer Inst.

Buffalo, New York, United States

Site Status

New York University Cancer Cen

New York, New York, United States

Site Status

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Site Status

Willamette Valley Cancer Ctr - 520 Country Club

Eugene, Oregon, United States

Site Status

Oregon Health Sciences Uni

Portland, Oregon, United States

Site Status

Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

Nashville, Tennessee, United States

Site Status

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Site Status

Texas Transplant Inst.

San Antonio, Texas, United States

Site Status

Texas Oncology, P.A. - Tyler; Tyler Cancer Center

Tyler, Texas, United States

Site Status

Fairfax N Virginia Hem/Onc PC

Fairfax, Virginia, United States

Site Status

Oncology & Hematolgy Associates of SW Va Inc. - Roanoke

Roanoke, Virginia, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, United States

Site Status

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

Site Status

Univ of Wisconsin-Madison

Madison, Wisconsin, United States

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Site Status

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, Canada

Site Status

Hopital Claude Huriez - CHU Lille

Lille, , France

Site Status

CHU Montpellier - Saint ELOI

Montpellier, , France

Site Status

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Centre Henri Becquerel; Hematologie

Rouen, , France

Site Status

Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V

Heidelberg, , Germany

Site Status

Universitätsmedizin Johannes Gutenberg Universität; Klinik u. Poliklinik f. Neurologie

Mainz, , Germany

Site Status

Klinikum d.Universität München Campus Großhadern

München, , Germany

Site Status

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

Bologna, Emilia-Romagna, Italy

Site Status

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, Italy

Site Status

Azienda Ospedale San Giovanni

Turin, Piedmont, Italy

Site Status

Academisch Medisch Centrum; Hematologie

Amsterdam, , Netherlands

Site Status

Countries

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United States Canada France Germany Italy Netherlands

References

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Shi R, Lu T, Ku G, Ding H, Saito T, Gibiansky L, Agarwal P, Li X, Jin JY, Girish S, Miles D, Li C, Lu D. Asian race and origin have no clinically meaningful effects on polatuzumab vedotin pharmacokinetics in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020 Sep;86(3):347-359. doi: 10.1007/s00280-020-04119-8. Epub 2020 Aug 8.

Reference Type DERIVED
PMID: 32770353 (View on PubMed)

Lu T, Gibiansky L, Li X, Li C, Shi R, Agarwal P, Hirata J, Miles D, Chanu P, Girish S, Jin JY, Lu D. Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2020 Dec;61(12):2905-2914. doi: 10.1080/10428194.2020.1795154. Epub 2020 Jul 24.

Reference Type DERIVED
PMID: 32705923 (View on PubMed)

Morschhauser F, Flinn IW, Advani R, Sehn LH, Diefenbach C, Kolibaba K, Press OW, Salles G, Tilly H, Chen AI, Assouline S, Cheson BD, Dreyling M, Hagenbeek A, Zinzani PL, Jones S, Cheng J, Lu D, Penuel E, Hirata J, Wenger M, Chu YW, Sharman J. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5):e254-e265. doi: 10.1016/S2352-3026(19)30026-2. Epub 2019 Mar 29.

Reference Type DERIVED
PMID: 30935953 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2011-004377-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO27834

Identifier Type: -

Identifier Source: org_study_id

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