Study to Evaluate the Safety and Efficacy of KITE-585 in Participants With Relapsed/Refractory Multiple Myeloma

Purpose

The primary objective of the study is to evaluate the safety and tolerability of KITE-585, an autologous engineered chimeric antigen receptor (CAR) T-cell product targeting a protein commonly found on myeloma cells called B-cell maturation antigen (BCMA), as measured by the incidence of dose-limiting toxicities (DLTs). Participants will be given a 3 day course of conditioning chemotherapy followed by a single infusion of KITE-585.

Condition

  • Relapsed/Refractory Multiple Myeloma

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Measurable relapsed or refractory myeloma as defined by the International Myeloma Working Group (IMWG) Consensus Criteria following treatment with at least 3 lines of therapy including with both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or progressive myeloma that is refractory to a regimen containing both a PI and an IMiD.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  3. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
  4. Absolute neutrophil count (ANC) ≥ 1,000/µL
  5. Platelet count ≥ 75,000/µL
  6. Absolute lymphocyte count ≥ 100/µL
  7. Creatinine clearance above limits set in the protocol for each cohort
  8. Normal cardiac function as assessed by electrocardiogram (ECG) and echocardiogram
  9. Baseline oxygen saturation > 92% on room air and no clinically significant pleural effusion

Exclusion Criteria

  1. Plasma cell leukemia
  2. Non-secretory multiple myeloma
  3. History of Central nervous system (CNS) involvement by multiple myeloma
  4. Prior CAR therapy or other genetically modified T cells
  5. Inadequate washout from prior therapy
  6. Autologous stem cell transplant within 6 weeks before enrollment or any history of allogenic transplant
  7. History of active autoimmune disease
  8. History of deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment
  9. Recent history of other (non multiple myeloma) cancer
  10. Active viral, fungal, bacterial or other infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Dose-Escalation and Dose Expansion
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation: 3 x 10^7 KITE-585
Participants with relapsed/refractory multiple myeloma (RRMM), will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of KITE-585 autologous anti-B-cell maturation antigen (BCMA) CAR T cells at a dose of 3 x 10^7 3e7 transduced cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
  • Genetic: KITE-585
    A single infusion of KITE-585 autologous anti-BCMA CAR T cells
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Experimental
Dose Escalation: 1 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 anti-autologous BCMA CAR T cells at a dose of 1 x 10^8 3e7 transduced cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
  • Genetic: KITE-585
    A single infusion of KITE-585 autologous anti-BCMA CAR T cells
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Experimental
Dose Escalation: 3 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 anti-autologous BCMA CAR T cells at a dose of 3 x 10^8 3e7 transduced cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
  • Genetic: KITE-585
    A single infusion of KITE-585 autologous anti-BCMA CAR T cells
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Experimental
Dose Escalation: 1 x 10^9 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 anti-autologous BCMA CAR T cells at a dose of 1 x 10^9 3e7 transduced cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
  • Genetic: KITE-585
    A single infusion of KITE-585 autologous anti-BCMA CAR T cells
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Experimental
Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585
RRMM participants with moderate renal impairment (creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) will receive a conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 24 mg/m^2/day IV infusion for 3 days followed by a single intravenous infusion of KITE-585 anti-autologous BCMA CAR T cells at a tolerable dose of 3 x 10^7 3e7 transduced cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants then had a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
  • Genetic: KITE-585
    A single infusion of KITE-585 autologous anti-BCMA CAR T cells
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously

More Details

Status
Active, not recruiting
Sponsor
Kite, A Gilead Company

Study Contact

Detailed Description

Participants with relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, ECG and echocardiogram of the heart, brain MRI, and blood draws. Eligible participants have white blood cells collected by leukapheresis. These cells are genetically modified to make the experimental treatment KITE-585. Participants receive conditioning chemotherapy prior to the KITE-585 infusion. After the KITE-585 infusion, participants will be followed for side effects and effect of KITE-585 on their myeloma. Study procedures may be performed while hospitalized and/or in the outpatient setting.