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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 currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01992653
First received: October 28, 2013
Last updated: September 1, 2015
Last verified: September 2015
  Purpose
This multicenter, open-label, dose-escalation study will evaluate the safety and anti-tumor activity of polatuzumab vedotin in combination with rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone in participants with non-Hodgkin's lymphoma. Cohort of participants will receive escalating doses of polatuzumab vedotin intravenously every 3 weeks in combination with standard doses of rituximab or obinutuzumab, cyclophosphamide, doxorubicin, and oral prednisone. 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 rituximab-prednisone/prednisolone, cyclophosphamide, and doxorubicin (R-CHP) and obinutuzumab-prednisone/prednisolone, cyclophosphamide, and doxorubicin (G-CHP). The maximum tolerated dose (MTD) of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD is determined, polatuzumab vedotin will be dosed at MTD -1 in combination with G-CHP to start the dose escalation of this combination. Two parallel treatment arms will explore doses of polatuzumab vedotin in combination with R-CHP and G-CHP. The MTD of polatuzumab vedotin in combination with R-CHP will be identified before it is combined with G-CHP. Once the MTD is determined, polatuzumab vedotin will be dosed at MTD -1 in combination with G-CHP to start the dose escalation of this combination.

Condition Intervention Phase
Lymphoma, B-Cell, Non-Hodgkin's Lymphoma
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Obinutuzumab
Drug: Polatuzumab Vedotin
Drug: Prednisone/Prednisolone
Drug: Rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE Ib/II STUDY EVALUATING THE SAFETY, TOLERABILITY AND ANTI-TUMOR ACTIVITY OF POLATUZUMAB VEDOTIN 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:
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 40 weeks ] [ Designated as safety issue: No ]
  • Safety: Incidence of anti-polatuzumab vedotin antibodies [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of anti-obinutuzumab antibodies [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patient-reported outcome of peripheral neuropathy symptom severity and symptom interference, as \nmeasured by the Therapy-Induced Neuropathy Assessment Scale (TINAS) [ Time Frame: once a week for the first 2 months, then once a month for the next 10 months following treatment completion ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum concentration (Cmax) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Clearance (CL) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Terminal half-life (t1/2) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Steady-state volume of distribution (Vss) [ Time Frame: Participants will be followed through four cycles of treatment, for an expected average of 12 weeks. ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: November 2013
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polatuzumab Vedotin + G-CHP
Participants will receive prednisone/prednisolone (100 mg) per oral (PO) along with obinutuzumab (1000 milligrams [mg]) intravenous (IV) followed by cyclophosphamide (750 milligrams per meter square [mg/m^2]) IV and doxorubicin (50 mg/m^2) IV on Cycle 1-2 Day 1 as per institutional practice. Participants will receive G-CHP (prednisone/prednisolone [100 mg PO], cyclophosphamide [750 mg/m^2 IV] and doxorubicin [50 mg/m^2 IV]) on Cycle 1 Day 8 and Day 15 followed by prednisone/prednisolone (100 mg PO) and polatuzumab vedotin IV infusions along with obinutuzumab (1000 mg IV) on Cycle 1-2 Day 2. Thereafter G-CHP and polatuzumab vedotin IV infusions will be given on a single day for Cycles 3-6 as per institutional practice.
Drug: Cyclophosphamide
Cyclophosphamide will be administered at 750 mg/m^2 IV every 3 weeks, for 6 or 8 cycles.
Drug: Doxorubicin
Doxorubicin will be administered at 50 mg/m2 IV every 3 weeks, for 6 or 8 cycles.
Drug: Obinutuzumab
Obinutuzumab will be administered at 1000 mg IV every 3 weeks, for 6 or 8 cycles.
Drug: Polatuzumab Vedotin
Polatuzumab vedotine will be administered at escalating doses IV every 3 weeks, for 6 or 8 cycles.
Drug: Prednisone/Prednisolone
Prednisone/prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks, for 6 or 8 cycles.
Experimental: Polatuzumab Vedotin + R-CHP
Participants will receive prednisone/prednisolone (100 mg) PO along with rituximab (375 mg/m^2) IV followed by cyclophosphamide (750 mg/m^2) IV and doxorubicin (50 mg/m^2) IV on Cycle 1-2 Day 1 as per institutional practice. Participants will receive prednisone/prednisolone (100 mg) PO on Cycle 1-2 Day 2 followed by IV polatuzumab vedotin (dose which will depend on the dose level assignment and the participant's weight on Day 1 of Cycle 1). Thereafter R-CHP (prednisone/prednisolone [100 mg PO], cyclophosphamide [750 mg/m^2 IV] and doxorubicin [50 mg/m^2 IV]) and polatuzumab vedotin IV infusions will be given on a single day for Cycles 3-6.
Drug: Cyclophosphamide
Cyclophosphamide will be administered at 750 mg/m^2 IV every 3 weeks, for 6 or 8 cycles.
Drug: Doxorubicin
Doxorubicin will be administered at 50 mg/m2 IV every 3 weeks, for 6 or 8 cycles.
Drug: Polatuzumab Vedotin
Polatuzumab vedotine will be administered at escalating doses IV every 3 weeks, for 6 or 8 cycles.
Drug: Prednisone/Prednisolone
Prednisone/prednisolone will be administered at 100 mg orally daily for 5 days every 3 weeks, for 6 or 8 cycles.
Drug: Rituximab
Rituximab will be administered at 375 mg/m^2 IV every 3 weeks, for 6 or 8 cycles.
Other Name: MabThera/Rituxan

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All Participants:

  • Adult participants, 60 to 80 years of age, inclusive
  • At least one bi-dimensionally measurable lesion, defined as greater than (>) 1.5 centimeter (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)

Dose-Escalation Portion of the Study:

  • Histologically confirmed B-cell non-Hodgkin's lymphoma (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-CD20 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)
  • Age-adjusted-International Prognostic Index score of 2-3

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 >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
  • 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)
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01992653

Contacts
Contact: Reference Study ID Number: GO29044 www.roche.com/about_roche/roche_worldwide.htm, han 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Alabama
Recruiting
Birmingham, Alabama, United States, 35233
United States, Arizona
Not yet recruiting
Gilbert, Arizona, United States, 85234
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Missouri
Active, not recruiting
St Louis, Missouri, United States, 63110
United States, Oregon
Recruiting
Portland, Oregon, United States, 97210
Active, not recruiting
Portland, Oregon, United States, 97239
Recruiting
Springfield, Oregon, United States, 97477
United States, Virginia
Not yet recruiting
Blacksburg, Virginia, United States, 24060
United States, Washington
Recruiting
Tacoma, Washington, United States, 98405
France
Recruiting
Creteil, France, 94010
Recruiting
Lille, France, 59037
Terminated
Pessac, France, 33604
Recruiting
Pierre Benite, France, 69495
Recruiting
Rennes, France, 35033
Recruiting
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 
Study First Received: October 28, 2013
Last Updated: September 1, 2015
Health Authority: United States: Food and Drug Administration

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
Prednisolone
Methylprednisolone Hemisuccinate
Prednisone
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

ClinicalTrials.gov processed this record on September 26, 2016