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A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01992653
First Posted: November 25, 2013
Last Update Posted: September 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
This multicenter, open-label, dose-escalation study will evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (CHP chemotherapy) in participants with non-Hodgkin's lymphoma (NHL). Participants will receive escalating doses of polatuzumab vedotin intravenously (IV) every 3 weeks in combination with standard doses of rituximab plus CHP chemotherapy (R-CHP) or obinutuzumab plus CHP chemotherapy (G-CHP). Participants will be treated for a total of six or eight cycles in accordance with local institutional practice. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP or G-CHP. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD or RP2D is determined, polatuzumab vedotin will be dosed at MTD or RP2D -1 in combination with G-CHP to start the dose escalation of this combination.

Condition Intervention Phase
Lymphoma, Non Hodgkin Drug: Cyclophosphamide Drug: Doxorubicin Drug: Obinutuzumab Drug: Polatuzumab Vedotin Drug: Prednisolone Drug: Prednisone Drug: Rituximab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study Evaluating the Safety, Tolerability and Anti-Tumor Activity of Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 6 years ]
  • Percentage of Participants with Dose Limiting Toxicities [ Time Frame: Cycle (Cy) 1 Day 1 (D1) to Cy 2 D1 (cycle length=21 days) ]
  • Maximum Tolerated Dose (MTD) of Polatuzumab Vedotin [ Time Frame: Cy 1 D1 to Cy 2 D1 (cycle length=21 days) ]

Secondary Outcome Measures:
  • Percentage of Participants with Objective Response (CR or Partial Response [PR]), as Assessed by Investigator using Cheson Criteria [ Time Frame: At the end of treatment (Month 6) ]
  • Percentage of Participants with Anti-Polatuzumab Vedotin Antibodies [ Time Frame: Baseline up to Month 9 (assessed prior to polatuzumab vedotin infusion [0 hour; Hr] on Day 2 [D2] of Cy 1 and 2, D1 of Cy 4, treatment completion/early termination [Month 6], and at 3 months post-treatment [Month 9]; cycle length=21 days) ]
  • Percentage of Participants with Anti-Obinutuzumab Antibodies [ Time Frame: Baseline up to Month 9 (assessed prior to obinutuzumab infusion [0 Hr] on D1 of Cy 1, 2, 4 and at 3 months post-treatment [Month 9]; cycle length=21 days) ]
  • Area Under the Concentration-Time Curve of Polatuzumab Vedotin [ Time Frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 minutes (min) post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) ]
  • Maximum concentration (Cmax) of Polatuzumab Vedotin [ Time Frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) ]
  • Clearance (CL) of Polatuzumab Vedotin [ Time Frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) ]
  • Terminal Half-Life (t1/2) of Polatuzumab Vedotin [ Time Frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) ]
  • Steady-State Volume of Distribution (Vss) of Polatuzumab Vedotin [ Time Frame: Pre-polatuzumab vedotin infusion (Hr 0), 30 min post-infusion (infusion time=30-90 min) on D 2 of Cy 1, 2 & D1 of Cy 3, 4; Cy 1 Days 8 & 15; Cy 3 Day 8; at end of treatment (Month 6), at Month 3 follow-up (Month 9) (cycle length=21 days) ]
  • Plasma Levels of Cyclophosphamide [ Time Frame: End of cyclophosphamide infusion (infusion time=1-24 Hr), 3 and 23 hours post end of cyclophosphamide infusion on D1 of Cy 1 and 3 (cycle length=21 days) ]
  • Plasma Levels of Doxorubicin [ Time Frame: 2, 24 hours post end of doxorubicin infusion (infusion time=15 min) on D1 of Cy 1 and 3 (cycle length=21 days) ]
  • Percentage of Participants with Complete Response (CR), as Assessed by Investigator using Cheson Criteria [ Time Frame: At the end of treatment (Month 6) ]
  • Peripheral Neuropathy Symptom Severity: Therapy-Induced Neuropathy Assessment Scale (TINAS) Overall Neuropathy Severity Score [ Time Frame: Weekly (up to Month 8), and then monthly for 10 months (up to Month 18) ]
  • Peripheral Neuropathy Symptom Interference: TINAS Numbness/Tingling Item Score [ Time Frame: Weekly (up to Month 8), and then monthly for 10 months (up to Month 18) ]
  • Duration of Response, as Assessed by Investigator Using Cheson Criteria [ Time Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
  • Progression Free Survival, as Assessed by Investigator Using Cheson Criteria [ Time Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
  • Event Free Survival, as Assessed by Investigator Using Cheson Criteria [ Time Frame: Screening up to disease progression or death, whichever occurs first (up to approximately 2.75 years) ]
  • Relative Dose Intensity of Polatuzumab Vedotin (Ratio of the Amount of Drug Actually Administered to the Amount Planned) [ Time Frame: 6 months ]
  • Overall Survival [ Time Frame: Screening up to death due to any cause (up to approximately 6 years) ]

Enrollment: 85
Actual Study Start Date: November 29, 2013
Estimated Study Completion Date: December 27, 2018
Estimated Primary Completion Date: December 27, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polatuzumab Vedotin + G-CHP
Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with G-CHP.
Drug: Cyclophosphamide
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Drug: Doxorubicin
Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Drug: Obinutuzumab
Obinutuzumab will be administered at 1000 milligrams (mg) IV on Cycle 1 Days 1, 8, and 15 and on Day 1 of Cycles 3-8.
Other Name: Gazyva/Gazyvaro
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
Other Name: DCDS4501A
Drug: Prednisolone
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Drug: Prednisone
Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Experimental: Polatuzumab Vedotin + R-CHP
Participants will receive a total of six to eight 21-day cycles of polatuzumab vedotin in combination with R-CHP.
Drug: Cyclophosphamide
Cyclophosphamide will be administered at 750 milligrams per square meter (mg/m^2) IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Drug: Doxorubicin
Doxorubicin will be administered at 50 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Drug: Polatuzumab Vedotin
Polatuzumab vedotin will be administered at escalating doses (at a starting dose of 1 mg/kg) IV every 3 weeks, for 6 or 8 cycles.
Other Name: DCDS4501A
Drug: Prednisolone
Prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Drug: Prednisone
Prednisone will be administered at 100 mg orally daily for 5 days every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles. Prednisone at 100 mg orally from Day -7 to Day -1 may be given at the discretion of the treating investigator physician.
Drug: Rituximab
Rituximab will be administered at 375 mg/m^2 IV every 3 weeks (starting from Cycle 1 Day 1), for 6 or 8 cycles.
Other Name: MabThera/Rituxan

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

All Participants:

  • At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeters (cm) in its longest dimension
  • Life expectancy of at least 24 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Adequate hematologic function (unless inadequate function is due to underlying disease, as established by extensive bone marrow involvement or is due to hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)
  • Agreement to use highly effective contraception measures. Women of childbearing potential must agree to remain abstinent or use contraceptive measures that result in a failure rate of <1 percent (%) per year during the treatment period and for at least 12 months for R-CHP arm or for at least 18 months for G-CHP arm after the last dose of study drug. Men must agree to remain abstinent or to use a condom plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of study drug

Dose-Escalation Portion of the Study:

  • Histologically confirmed B-cell NHL: Participants with newly diagnosed B-cell NHL or relapsed/refractory B-cell NHL are eligible
  • No more than one prior systemic treatment regimen for B-cell NHL (single agent anti-cluster of differentiation [CD] 20 monoclonal antibody therapy will not be counted as a prior treatment regimen)
  • No prior treatment with anthracyclines

Expansion Portion of the Study:

  • Previously untreated participants with diffuse large B-cell lymphoma (DLBCL)
  • International Prognostic Index score of 2-5

Exclusion Criteria:

Dose-Escalation Portion of the Study:

  • Diagnosis of primary mediastinal DLBCL

Expansion Portion of the Study:

  • Participants with transformed lymphoma
  • Prior therapy for NHL

All Participants:

  • Prior stem cell transplant
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
  • Contraindication to receive any of the individual components of R-CHP or G-CHP
  • Current Grade greater than (>) 1 peripheral neuropathy
  • Ongoing corticosteroid use of >30 milligrams per day (mg/day) of prednisone/prednisolone or equivalent. Participants receiving corticosteroid treatment with less than or equal to (</=) 30 mg/day of prednisone//prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration before Cycle 1 Day 1
  • Primary central nervous system (CNS) lymphoma
  • Vaccination with live vaccines within 6 months before Cycle 1 Day 1
  • History of other malignancy that could affect compliance with the protocol or interpretation of results. Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible. Participants with a malignancy that has been treated with surgery alone with curative intent will also be excluded unless the malignancy has been in documented remission without treatment for greater than or equal to (</=) 5 years before enrollment
  • Evidence of significant, uncontrolled concomitant diseases, including renal disease that would preclude chemotherapy administration, or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
  • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks before Cycle 1 Day 1
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Positive for hepatitis B or hepatitis C infection
  • Prior radiotherapy to the mediastinal/pericardial region
  • Pregnant or lactating women
  • Recent major surgery within 6 weeks before the start of Cycle 1 Day 1
  • Abnormal laboratory values
  Contacts and Locations
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): NCT01992653


Locations
United States, Alabama
The University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arizona
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University; Pediatrics
Saint Louis, Missouri, United States, 63110
United States, Oregon
Northwest Cancer Specialists
Portland, Oregon, United States, 97210
Oregon Health and Science University
Portland, Oregon, United States, 97239
Willamette Valley Clinical Studies; Cancer Institute
Springfield, Oregon, United States, 97477
United States, Texas
Cancer Care Centers of South Texas
San Antonio, Texas, United States, 78212
United States, Virginia
Blue Ridge Cancer Care
Roanoke, Virginia, United States, 24014
United States, Washington
Northwest Medical Specialties, PLLC; Research Department
Tacoma, Washington, United States, 98405
France
Hopital Henri Mondor, Unite Hemopathies lymphoides
Creteil, France, 94010
Hopital Claude Huriez - CHU Lille; Service des maladies du sang
Lille, France, 59037
Hopital Haut-Leveque - Centre Francois Magendie; Service d'Hematologie Clinique
Pessac, France, 33604
Centre Hospitalier Lyon Sud; Hematolgie
Pierre Benite, France, 69495
Hopital Pontchaillou - CHU de Rennes
Rennes, France, 35033
Centre Henri Becquerel; Hematologie
Rouen, France, 76038
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01992653     History of Changes
Other Study ID Numbers: GO29044
2013-003541-42 ( EudraCT Number )
First Submitted: October 28, 2013
First Posted: November 25, 2013
Last Update Posted: September 12, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Obinutuzumab
Doxorubicin
Prednisone
Prednisolone
Methylprednisolone Hemisuccinate
Antibodies, Monoclonal
Immunoconjugates
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents