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

NCT ID: NCT03318861

Last Updated: 2023-10-19

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-20

Study Completion Date

2022-09-16

Brief Summary

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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

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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

Conditions

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Relapsed/Refractory Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose-Escalation and Dose Expansion
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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 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.

Group Type EXPERIMENTAL

KITE-585

Intervention Type GENETIC

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

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 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.

Group Type EXPERIMENTAL

KITE-585

Intervention Type GENETIC

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

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 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.

Group Type EXPERIMENTAL

KITE-585

Intervention Type GENETIC

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

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 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.

Group Type EXPERIMENTAL

KITE-585

Intervention Type GENETIC

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

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 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.

Group Type EXPERIMENTAL

KITE-585

Intervention Type GENETIC

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Cyclophosphamide

Intervention Type DRUG

Administered intravenously

Fludarabine

Intervention Type DRUG

Administered intravenously

Interventions

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KITE-585

A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Intervention Type GENETIC

Cyclophosphamide

Administered intravenously

Intervention Type DRUG

Fludarabine

Administered intravenously

Intervention Type DRUG

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kite, A Gilead Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

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David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 34249462 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Amendment 2

View Document

Document Type: Study Protocol: Amendment 3

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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KITE-585-501

Identifier Type: -

Identifier Source: org_study_id

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