Clinical Trials /

A Study Evaluating Safety and Efficacy of Obinutuzumab, Polatuzumab Vedotin (Pola), and Atezolizumab (Atezo) in Participants With Relapsed or Refractory Follicular Lymphoma (FL) and Rituximab, Atezo, and Pola in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

NCT02729896

Description:

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab + Atezo + Pola in participants with relapsed or refractory (RR) FL and rituximab + Atezo + Pola in participants with RR DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for Pola in this treatment combination, followed by an expansion phase in which Pola will be given at the RP2D. All participants will receive induction treatment with obinutuzumab + Atezo + Pola for 6 cycles. RR FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) will receive maintenance treatment with obinutuzumab.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title:A Study of Obinutuzumab, Polatuzumab Vedotin, and Atezolizumab in Relapsed or Refractory Follicular Lymphoma (FL) or Diffuse Large B-Cell Lymphoma (DLBCL)
  • Official Title:A PHASE Ib/II STUDY EVALUATING THE SAFETY AND EFFICACY OF OBINUTUZUMAB IN COMBINATION WITH ATEZOLIZUMAB PLUS POLATUZUMAB VEDOTIN IN PATIENTS WITH RELAPSED OR REFRACTORY FOLLICULAR LYMPHOMA OR DIFFUSE LARGE B CELL LYMPHOMA

Clinical Trial IDs

  • ORG STUDY ID: BO29561
  • SECONDARY ID: 2015-004845-25
  • NCT ID: NCT02729896

Trial Conditions

  • Lymphoma

Trial Interventions

DrugSynonymsArms
AtezolizumabDose-Escalation Phase
ObinutuzumabDose-Escalation Phase
Polatuzumab VedotinDose-Escalation Phase

Trial Purpose

This study will evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of obinutuzumab (G) + atezolizumab (Atezo) + polatuzumab vedotin (Pola) in participants with relapsed or refractory FL or DLBCL. The study will include an initial dose-escalation phase designed to determine the recommended Phase 2 dose (RP2D) for polatuzumab vedotin in this treatment combination, followed by an expansion phase in which polatuzumab vedotin will be given at the RP2D. All participants will receive induction treatment with G + Atezo + Pola for 6 cycles. FL participants achieving a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOI) and DLBCL participants achieving a CR or PR at EOI will be eligible to receive post-induction treatment with obinutuzumab + atezolizumab.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Dose-Escalation PhaseExperimentalDuring the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and polatuzumab vedotin on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, atezolizumab on Day 1, and polatuzumab vedotin on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 and atezolizumab on Days 1 and 2 of each month for 24 months, during maintenance treatment for FL participants.
  • Atezolizumab
  • Obinutuzumab
  • Polatuzumab Vedotin
Expansion PhaseExperimentalDuring the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and polatuzumab vedotin at identified RP2D (decided from dose escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, atezolizumab on Day 1, and polatuzumab vedotin at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 and atezolizumab on Days 1 and 2 of each month for 24 months (during maintenance treatment for FL participants) and for 8 months (during consolidation treatment for DLBCL participants).
  • Atezolizumab
  • Obinutuzumab
  • Polatuzumab Vedotin

Eligibility Criteria

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) A21 Status of 0, 1, or 2

- For participants enrolled in the dose-escalation phase: relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator

- For participants enrolled in the expansion phase: lymphoma classified as either relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which not other more appropriate treatment option exists as determined by the investigator OR classified as Relapsed or refractory DLBCL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody, in patients who are not eligible for second line combination chemotherapy and autologous stem-cell transplantation or who have failed second line combination chemotherapy or experienced disease progression following autologous stem-cell transplantation

- Histologically documented CD20-positive lymphoma and fluorodeoxyglucose (FDG)-avid lymphoma (that is positron emission tomography [PET]-positive lymphoma) with at least one bi-dimensionally measurable lesion

- Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL

- For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or to use contraceptive methods that result in a failure rate of <1% per year during the treatment period for >= 18 months after the last dose of obinutuzumab

- For men: agreement to remain abstinent or to use contraceptive measures that result in a failure rate of <1% per year during the treatment period and for at least 5 months after last dose of study drug, and agreement to refrain from donating sperm during this same period

Exclusion Criteria:

- Grade 3b follicular lymphoma

- History of transformation of indolent disease to DLBCL

- Known CD20-negative status at relapse or progression; central nervous system (CNS) lymphoma or leptomeningeal infiltration

- Prior allogeneic stem cell transplantation (SCT), completion of autologous SCT within 100 days prior to Day 1 of Cycle 1 (D1C1)

- Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 months prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti programmed cell death protein 1 (anti PD-1), anti programmed death-ligand 1 (PD-L1), anti cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti CD137/41-BB agonist, or anti-CD40 agonist antibodies

- Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to D1C1

- History of solid organ transplantation and of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies

- Active infection; positive for hepatitis B surface agent (HbsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening; known history of HIV positive status, progressive multifocal leukoencephalopathy (PML), autoimmune disease

- Vaccination with a live virus vaccine or live attenuated vaccine within 28 days prior to D1C1

- Pre-existing Grade > 1 neuropathy

- Major surgical procedure other than for diagnosis within 28 days prior to D1C1

- Inadequate hematologic function, renal function, and liver function

- Pregnant or lactating women

- Life expectancy less than (<) 3 months

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II Dose (RP2D) of Polatuzumab Vedotin in Combination With Fixed Doses of Obinutuzumab and Atezolizumab
Time Frame:6 months
Safety Issue:Yes
Description:

Secondary Outcome Measures

Measure:Percentage of Participants With Complete Response (CR) at EOI, as Determined by Investigator on the Basis of positron emission tomography and computed tomography (PET-CT) Scan
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:No
Description:
Measure:Percentage of Participants With Complete Response (CR) at EOI, as Determined by IRC and Investigator on the Basis of CT Scan
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:No
Description:
Measure:Percentage of Participants with Objective Response (CR + PR) at EOI, as Determined by the IRC and by the Investigator on the basis of PET-CT Scan
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:No
Description:
Measure:Percentage of Participants with Objective Response (CR + PR) at EOI, as determined by the IRC and by the Investigator on the basis of CT Scan
Time Frame:Within 6 to 8 weeks after Day 1 of Cycle 6 (up to approximately 6 months)
Safety Issue:No
Description:
Measure:Percentage of Participants With Best Overall Response, as Determined by the Investigator on the Basis of CT Scan
Time Frame:approximately 30 months
Safety Issue:No
Description:

Trial Keywords