Clinical trial NCT03318861: Study to Evaluate the Safety and Efficacy of KITE-585 in Participants With Relapsed/Refractory Multiple Myeloma
Official title: A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA CAR T-Cell Therapy, in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose-Escalation and Dose Expansion
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: From KITE-585 infusion until 28 days after KITE-585 infusion
Secondary outcomes:
measure: Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria
timeFrame: 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)
measure: Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: From KITE-585 infusion to date of data cutoff (maximum: 17.6 months)
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: 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)
measure: Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities
timeFrame: 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)
measure: Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1
timeFrame: 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)
measure: Time to Next Treatment (TTNT)
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References:
citation: Cornell RF, Bishop MR, Kumar S, Giralt SA, Nooka AK, Larson SM, Locke FL, Raje NS, Lei L, Dong J, Le Gall JB, Rossi JM, Orlowski RZ. A phase 1, multicenter study evaluating the safety and efficacy of KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma. Am J Cancer Res. 2021 Jun 15;11(6):3285-3293. eCollection 2021.