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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)

This study has suspended participant recruitment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02431208
First Posted: April 30, 2015
Last Update Posted: November 7, 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):
Hoffmann-La Roche
April 27, 2015
April 30, 2015
November 7, 2017
July 22, 2015
September 26, 2020   (Final data collection date for 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) ]
  • Recommended Phase II Dose (RP2D) of Lenalidomide in the Combinations Tested [ Time Frame: From start of treatment until 30 days after last dose (up to approximately 36 months) ]
  • RP2D of Pomalidomide in the Combinations Tested [ Time Frame: From start of treatment until 30 days after last dose (up to approximately 36 months) ]
  • Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: From start of treatment until 30 days after last dose (up to approximately 36 months) ]
  • Determination of recommended Phase II dose of MPDL3280A administered in combination with lenalidomide [ Time Frame: Up to approximately 36 months ]
  • Incidence of adverse events [ Time Frame: Up to approximately 36 months ]
Complete list of historical versions of study NCT02431208 on ClinicalTrials.gov Archive Site
  • Duration of Response (DOR) According to IMWG Criteria [ Time Frame: From first observed response until the date of first recorded progression or death from any cause (up to 36 months overall) ]
  • Progression-Free Survival (PFS) According to IMWG Criteria [ Time Frame: From start of treatment until the date of first recorded progression or death from any cause (up to 36 months overall) ]
  • Percentage of Participants with Objective Response According to IMWG Criteria [ Time Frame: From Day 1 of Cycle 2 until progression, withdrawal, or study end (up to 36 months overall). For Cohort D3 Only: 6, 9, and 12 months. ]
  • Overall Survival [ Time Frame: From start of treatment until death from any cause (up to 36 months overall) ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: From predose (0 hours [h]) on Day 1 of Cycle 1 until treatment discontinuation (up to 36 months overall); see Outcome Measure Description for details ]
    Predose (0 h) and postdose (0.5 h) (infusion = 0.5-1 h) on Day 1 of Cycles 1, 3 (cycle = 21 or 28 days) and Day 2 of Cycle 1; predose (0 h) on Day 1 of Cycles 2, 4, 8; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)
  • Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 21 or 28 days) and Day 2 of Cycle 1; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall) ]
  • Cmax of Lenalidomide [ Time Frame: Predose (0 h) and postdose (1 h) on Day 1 of Cycles 1, 4 (cycle = 21 days); predose (0 h) and postdose (0.5, 1, 2, 4, 8 h) on Day 15 of Cycles 1, 3; predose (0 h) and postdose (2 h) on Day 15 of Cycles 2, 4, 8 ]
  • Cmin of Lenalidomide [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 4 (cycle = 21 days) and Day 15 of Cycles 1, 2, 3, 4, 8 ]
  • Cmax of Pomalidomide [ Time Frame: Predose (0 h) and postdose (1, 2, 4, 6, 8 h) on Day 15 of Cycles 1, 3 (cycle = 28 days); predose (0 h) and postdose (4 h) on Day 15 of Cycles 2, 4, 8 ]
  • Cmin of Pomalidomide [ Time Frame: Predose (0 h) on Day 15 of Cycles 1, 2, 3, 4, 8 (cycle = 28 days) ]
  • Cmax of Daratumumab [ Time Frame: From predose (0 h) on Day 1 of Cycle 1 until treatment discontinuation (up to 36 months overall); see Outcome Measure Description for details ]
    Predose (0 h) and postdose (0.5 h) (infusion ~3-6 h) on Day 1 of Cycles 1, 3 (cycle = 28 days); predose (0 h) on Day 1 of Cycles 2, 4, 8; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)
  • Cmin of Daratumumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 28 days); then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall) ]
  • Change in Number of Participants With Anti-Drug Antibody (ADA) Response to Atezolizumab from Baseline to End of Study [ Time Frame: From treatment start until study end (up to 36 months overall); see Outcome Measure Description for details ]
    From treatment start until study end; assessed predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 21 or 28 days) and Day 2 of Cycle 1; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)
  • Change in Number of Participants With ADA Response to Daratumumab from Baseline to End of Study [ Time Frame: From treatment start until study end; assessed predose (0 h) on Day 1 of Cycles 1, 3, 8 (cycle = 28 days); at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall) ]
  • Pharmacokinetics: Serum maximum observed concentration (Cmax) of MPDL3280A [ Time Frame: Approximately 30 minutes post-infusion on Day 1 of Cycles 2, 3, 4, and 8 ]
  • Pharmacokinetics: Serum minimum observed concentration (Cmin) of MPDL3280A [ Time Frame: Prior to infusion on Day 1 of Cycles 1, 2, 3, 4, and 8 and every 8 cycles thereafter ]
  • Pharmacokinetics: Plasma Cmax of lenalidomide [ Time Frame: Approximately 1 hour post-infusion on Day 1 of Cycles 1 and 4 ]
  • Pharmacokinetics: Plasma Cmin of lenalidomide [ Time Frame: Prior to infusion on Day 1 of Cycles 1 and 4 ]
  • Pharmacokinetics: Incidence of anti-therapeutic antibody (ATA) response to MPDL3280A [ Time Frame: Up to approximately 36 months ]
  • Efficacy: Overall response rate (ORR) [ Time Frame: Up to approximately 36 months ]
  • Efficacy: Progression-free survival (PFS) [ Time Frame: Up to approximately 36 months ]
  • Efficacy: Duration of response (DOR) [ Time Frame: Up to approximately 36 months ]
Not Provided
Not Provided
 
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)
A Phase Ib Study of the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Patients With Multiple Myeloma (Relapsed/Refractory and Post-Autologous Stem Cell Transplantation)
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). The planned duration of this study is approximately 36 months. Cycle length will be 21 days in Cohorts A to C and 28 days in Cohorts D to F.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    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.
    Other Name: Tecentriq, MPDL3280A, "ATZ"
  • Drug: Daratumumab
    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.
    Other Name: Darzalex, "DAR"
  • Drug: Lenalidomide
    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.
    Other Name: Revlimid, "LEN"
  • Drug: Pomalidomide
    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.
    Other Name: Pomalyst, "POM"
  • 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.
    Intervention: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Lenalidomide
  • Experimental: Cohort C: ATZ + LEN (Post-ASCT)
    Cohort C will evaluate atezolizumab administered in combination with lenalidomide in participants with MM who have measurable disease after ASCT.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Lenalidomide
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
  • 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 up to 3 lines of prior treatment.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
    • Drug: Lenalidomide
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
    • Drug: Lenalidomide
  • 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
    • Drug: Pomalidomide
  • Experimental: 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.
    Interventions:
    • Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
    • Drug: Daratumumab
    • Drug: Pomalidomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
288
September 26, 2020
September 26, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Previous diagnosis of MM with objective evidence of measurable disease
  • Willing and able to undergo bone marrow aspiration and biopsy tissue sample collection during screening and on study
  • Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (</=) 2
  • Left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 40 percent (%)
  • Total bilirubin </=2 times the ULN
  • Creatinine </=2.0 milligrams per deciliter (mg/dL), with creatinine clearance (CrCl) using the Cockcroft-Gault formula >/=40 milliliters per minute (mL/min) or 60 mL/min for those who receive lenalidomide
  • Corrected calcium at or below ULN
  • Transaminase levels </=2.5 times the upper limit of normal (ULN)
  • Receipt of >/=1 but not more than 3 prior lines of therapy (Cohorts A, B, C, D1, D2, E)
  • Receipt of >/=2 prior lines of therapy and progressed on treatment with an anti-CD38 monoclonal antibody (Cohort D3)
  • Receipt of >/=4 lines of prior therapy (Cohort F)
  • Absolute neutrophil count (ANC) >/=1000 cells per microliter (cells/mcL) (Cohorts A, B, D, E, F)
  • Platelet count >/=50,000 cells/mcL, or >/=30,000 cells/mcL if more than 50% bone marrow involvement (Cohorts A, B, D, E, F)
  • All participants who are prescribed lenalidomide or pomalidomide must be counseled at a minimum of every 21-28 days about pregnancy precautions and risks of fetal exposure (Cohorts B, C, E, F)
  • Agree to be registered in and comply with all requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program (Cohorts B, C, E)
  • Agree to be registered in and comply with all requirements of the Pomalyst REMS program (Cohort F)
  • Sufficient recovery from first or second ASCT within 60-120 days of transplant (Cohort C)
  • Off antibiotic/antifungal therapy for >/=14 days (Cohort C)
  • Completion of any prior radiotherapy (Cohort C)
  • ANC >/=1500 cells/mcL (Cohort C)

Exclusion Criteria:

  • Other malignancy within 2 years prior to screening, with some exceptions
  • Prior therapy with atezolizumab or other immunotherapies including CD137 agonists, anti-programmed death (PD)-1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and anti-PD-L1 therapeutic antibodies
  • Uncontrolled cancer pain
  • Treatment with any investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer
  • Known hypersensitivity to study drug and/or drug class
  • History of autoimmune disease except for controlled, treated thyroidism or Type 1 diabetes
  • Prior systemic anti-myeloma therapy within 14 days of Cycle 1 Day 1
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome
  • Plasma cell leukemia (greater than 2,000 cells/mcL of circulating plasma cells by standard differential)
  • Immunosuppressive therapy within 6 weeks of Cycle 1 Day 1
  • Daily corticosteroid requirement within 2 weeks of Cycle 1 Day 1
  • Prior allogeneic stem cell transplant or solid organ transplant
  • Active hepatitis B, active hepatitis C, or positive for human immunodeficiency virus (HIV)
  • Uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis) that in the opinion of the investigator would put the participant at significant risk for pulmonary complications during the study
  • History of pneumonitis
  • Uncontrolled intercurrent illness including but not limited to uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or breastfeeding females
  • Inability to tolerate thromboprophylaxis (Cohorts B, C, E, F)
  • Evidence of progressive MM compared to pretransplant evaluation (Cohort C)
  • Prior treatment with anti-CD38 therapy including daratumumab (Cohorts D1, D2, E, F)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02431208
GO29695
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP