A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Participants With Multiple Myeloma (MM)

Conditions

• Multiple Myeloma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody — DRUG
  Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.
• Daratumumab — DRUG
  Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.
• Lenalidomide — DRUG
  Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1.
• Pomalidomide — DRUG
  Pomalidomide will be administered PO until loss of clinical benefit, withdrawal, or study end. Cohort F (combination with daratumumab) will receive 2 or 4 mg on Days 1-21 of each 28-day cycle. Participants in Cohort F1 will receive ascending-dose pomalidomide, and those in Cohort F2 will receive pomalidomide at the MTD as determined in Cohort F1.
• Dexamethasone — DRUG
  Participants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle.

Study Details

This multicenter, open-label, Phase I study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab alone or in combination with daratumumab and/or various immunomodulatory agents in participants with MM who have relapsed or who have undergone autologous stem cell transplantation (ASCT). Cycle length will be 21 days in Cohorts A to C and 28 days in Cohorts D to F.

Key Dates

Start date

Jul 22, 2015

Status verified

Mar 2021

Primary completion

Mar 19, 2021

Completion

Mar 19, 2021

Study Design

Enrollment

85 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort A: ATZ (Run-In)
  Cohort A will involve a safety run-in to evaluate atezolizumab administered as a single agent in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort has been completed.
• Experimental: Cohort B1: ATZ + LEN (Dose Escalation)
  Cohort B1 will involve a dose escalation to evaluate atezolizumab administered in combination with ascending-dose lenalidomide in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort has been completed.
• Experimental: Cohort C: ATZ + LEN (Post-ASCT):
  Cohort C will evaluate atezolizumab administered in combination with lenalidomide in participants with MM who have measureable disease after ASCT. NOTE: This cohort is closed to enrollment.
• Experimental: Cohort D1: ATZ + DAR (Run-in)
  Cohort D1 will involve a safety run-in to evaluate atezolizumab administered in combination with daratumumab in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment.
• Experimental: Cohort D2: ATZ + DAR (Expansion)
  Cohort D2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab in participants with relapsed or refractory MM who have received 2 but no more than 3 lines of prior treatment that must have included a PI and IMiD and are refractory to the last line of treatment.
• Experimental: Cohort D3: ATZ + DAR (Progressed)
  Cohort D3 will involve an expansion to evaluate atezolizumab in combination with daratumumab in participants with relapsed or refractory MM who have received 2 or more lines of prior treatment and have progressed with an anti-cluster of differentiation (CD) 38 monoclonal antibody, either alone or in combination, and are refractory to both a proteasome inhibitor (PI) and immunomodulatory drug (IMiD).
• Experimental: Cohort E1: ATZ + DAR + LEN (Dose Escalation)
  Cohort E1 will involve a dose escalation to evaluate atezolizumab administered in combination with daratumumab and ascending-dose lenalidomide in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort is closed to enrollment.
• Experimental: Cohort E2: ATZ + DAR + LEN (Expansion)
  Cohort E2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab and the maximum tolerated dose (MTD) of lenalidomide determined in Cohort E1 in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort is closed to enrollment.
• Experimental: Cohort F1: ATZ + DAR + POM (Dose Escalation)
  Cohort F1 will involve a dose escalation to evaluate atezolizumab administered in combination with daratumumab and ascending-dose pomalidomide in participants with relapsed or refractory MM who have received 4 or more lines of prior treatment and are refractory to the last line of treatment. NOTE: This cohort has been completed.
• Active Comparator: Cohort F2: ATZ + DAR + POM (Expansion)
  Cohort F2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab and the MTD of pomalidomide determined in Cohort F1 in participants with relapsed or refractory MM who have received 4 or more lines of prior treatment and are refractory to the last line of treatment. NOTE: This cohort is randomized.
• Active Comparator: Cohort F3: DAR + POM + Dexamethasone
  Cohort F3 is an expansion control arm for cohort F2. Participants will receive daratumumab in combination with pomalidomide at the MTD and dexamethasone. NOTE: This cohort is randomized.

Primary Outcome Measure

Percentage of Participants by Best Overall Response According to International Myeloma Working Group (IMWG) Criteria [ Time Frame: From Day 1 of Cycle 2 (cycle = 21 or 28 days) until progression, withdrawal, or study end (up to 36 months overall) ]

Locations (31)

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