Study to Evaluate the Safety and Efficacy of KITE-585 in Participants With Relapsed/Refractory Multiple Myeloma
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT03318861
- Lead Sponsor
- Kite, A Gilead Company
- Brief Summary
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.
- 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. 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 17
-
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.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
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
- Plasma cell leukemia
- Non-secretory multiple myeloma
- History of Central nervous system (CNS) involvement by multiple myeloma
- Prior CAR therapy or other genetically modified T cells
- Inadequate washout from prior therapy
- Autologous stem cell transplant within 6 weeks before enrollment or any history of allogenic transplant
- History of active autoimmune disease
- History of deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment
- Recent history of other (non multiple myeloma) cancer
- Active viral, fungal, bacterial or other infection
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585 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 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. Dose Escalation: 1 x 10^8 KITE-585 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 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. Dose Escalation: 3 x 10^8 KITE-585 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 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. Dose Escalation: 3 x 10^7 KITE-585 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 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. Dose Escalation: 1 x 10^9 KITE-585 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 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. Dose Escalation: 3 x 10^7 KITE-585 Fludarabine 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. Dose Escalation: 3 x 10^7 KITE-585 Cyclophosphamide 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. Dose Escalation: 1 x 10^8 KITE-585 Cyclophosphamide 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. Dose Escalation: 1 x 10^8 KITE-585 Fludarabine 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. Dose Escalation: 3 x 10^8 KITE-585 Cyclophosphamide 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. Dose Escalation: 3 x 10^8 KITE-585 Fludarabine 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. Dose Escalation: 1 x 10^9 KITE-585 Fludarabine 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. Dose Escalation: 1 x 10^9 KITE-585 Cyclophosphamide 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. Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585 Cyclophosphamide 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. Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585 Fludarabine 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) From KITE-585 infusion until 28 days after KITE-585 infusion A DLT is a KITE-585-related event with onset in the first 28 days following infusion. DLTs are defined by events and duration of events, including:
* Any duration: Grade (GR) 4 cytokine release syndrome (CRS), KITE-585-related GR 5 adverse events (AE) and GR 4 nonhematologic AE with the exceptions of fever, nausea, hepatic toxicity that resolves to GR 3 or better in ≤ 72 hours, hypogammaglobulinemia, tumor lysis syndrome, acute renal toxicity requiring dialysis for ≤ 7 days, intubation for airway protection for ≤ 7 days and AE resolves to ≤ GR 1 within 2 weeks and baseline within 4 weeks
* ≥ 72 hours: GR 3 CRS and GR 3 nonhematologic AE with the exceptions of fever, nausea, hepatic toxicity that resolves to GR 2 or better in ≤ 14 days, hypogammaglobulinemia and tumor lysis syndrome
* ≥ 30 days: GR 4 hematologic AE with the exceptions of cytopenias attributable to ongoing or recurrent multiple myeloma
- Secondary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-Emergent Adverse Events Enrollment through 24 months after treatment with KITE-585 or up to disease progression or initiation of another anti-cancer therapy, whichever occurs first (maximum: 2.9 months) Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1 From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months) PFS: Interval from first study drug dose date to the earlier of first documentation of definitive progressive disease (PD) per IMWG Consensus Panel 1 Criteria or death from any cause. PD: an increase of 25% from the lowest response value in 1 of the following: Serum and urine M-protein (absolute increase ≥ 0.5 g/dL and ≥ 200 mg/24 hours, respectively); In participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase \> 10 mg/dL); In participants without measurable serum and urine M-protein and without measurable disease by FLC levels, bone marrow PC percentage (absolute percentage ≥ 10%). Definite development of new bone lesions or STP or definite increase in the size of existing bone lesions or STPs; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder. Analysis was done using Kaplan-Meier (KM) estimate.
Overall Survival (OS) From KITE-585 infusion to date of data cutoff (maximum: 17.6 months) Overall survival is defined as the time from the first dose date of study drug to the date of death from any cause. Analysis was done using KM estimate. Participants who have not died by the analysis data cutoff date were censored at their last date known to be alive or cutoff date, whichever is earlier.
Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities Enrollment through 24 months after treatment with KITE-585 or up to disease progression or initiation of another anti-cancer therapy, whichever occurs first (maximum: 2.9 months) Clinically significant laboratory abnormalities were defined as per investigator's discretion.
Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months) ORR: Percentage of participants who achieved a stringent CR (sCR), complete response (CR), partial response (PR), or very good PR (VGPR), as determined by IMWG Consensus Panel 1 Criteria. sCR: CR+normal free light chain (FLC) ratio, no clonal cells in BM by immunohistochemistry or immunofluorescence; CR: negative immunofixation (IFX) on serum and urine, no soft tissue plasmacytomas (STP), \<5% plasma cells in bone marrow (BM); PR: ≥50% decrease of serum M-protein + 24hr urinary M-protein decrease by ≥90% or \<200 mg/24hr. If unmeasurable serum and urine M-protein; and serum-free light assay; requires ≥ 50% decrease in the difference between involved and uninvolved FLC levels / ≥ 50% reduction in plasma cells (PC), provided baseline BM PC percentage was ≥ 30%, respectively. If present at baseline, ≥ 50% reduction in the size of STP is also required; VGPR: serum and urine M-protein detected by IFX but not electrophoresis, \>90% in serum M-protein+urine, M-protein level \<100 mg/24hr.
Time to Next Treatment (TTNT) From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months) TTNT is defined as the length of time between the date of KITE-585 infusion to the date of initiation of the next therapy or death due to any cause, whichever is earlier.
Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1 From first response to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months) DOR is defined for participants who experience an objective response and is defined as the time from the date of their first objective response (which is subsequently confirmed) to PD per IMWG Consensus Panel 1 Criteria or death from any cause, whichever is earlier. Objective response is defined in Outcome measure 2.
Trial Locations
- Locations (9)
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Winship Cancer Institute, Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States