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

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Relapsed/Refractory Multiple Myeloma

Treatments: Drug: Fludarabine; Drug: Cyclophosphamide; Genetic: KITE-585

Study type: Interventional

Funder types: Industry

Identifiers

NCT03318861

KITE-585-501

Details and patient eligibility

About

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.

Full 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. Participants who received an infusion of KITE-585 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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:

   • Absolute neutrophil count (ANC) ≥ 1,000/µL
   • Platelet count ≥ 75,000/µL
   • Absolute lymphocyte count ≥ 100/µL
   • Creatinine clearance above limits set in the protocol for each cohort
   • Normal cardiac function as assessed by electrocardiogram (ECG) and echocardiogram
   • Baseline oxygen saturation > 92% on room air and no clinically significant pleural effusion

Key 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

17 participants in 5 patient groups

Dose Escalation: 3 x 10^7 KITE-585

Experimental group

Description:

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 at a dose of 3 x 10\^7 autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T 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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Genetic: KITE-585

Dose Escalation: 1 x 10^8 KITE-585

Experimental group

Description:

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 at a dose of 1 x 10\^8 autologous anti-BCMA CAR T 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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Genetic: KITE-585

Dose Escalation: 3 x 10^8 KITE-585

Experimental group

Description:

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 at a dose of 3 x 10\^8 autologous anti-BCMA CAR T 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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Genetic: KITE-585

Dose Escalation: 1 x 10^9 KITE-585

Experimental group

Description:

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 at a dose of 1 x 10\^9 autologous anti-BCMA CAR T 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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Genetic: KITE-585

Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585

Experimental group

Description:

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 infusion of KITE-585 at a tolerable dose of 3 x 10\^7 autologous anti-BCMA CAR T 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.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Genetic: KITE-585