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

NCT03318861 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: KITE-585-501
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 9

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

  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

  From KITE-585 infusion until 28 days after KITE-585 infusion

Secondary Outcomes (7)

• 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)

• 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)

• Overall Survival (OS)

  From KITE-585 infusion to date of data cutoff (maximum: 17.6 months)

• 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)

• 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)

Study Arms (5)

Dose Escalation: 3 x 10^7 KITE-585

EXPERIMENTAL

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.

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

Dose Escalation: 1 x 10^8 KITE-585

EXPERIMENTAL

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.

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

Dose Escalation: 3 x 10^8 KITE-585

EXPERIMENTAL

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.

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

Dose Escalation: 1 x 10^9 KITE-585

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

Interventions

KITE-585 GENETIC

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

Dose Escalation: 1 x 10^8 KITE-585; Dose Escalation: 1 x 10^9 KITE-585; Dose Escalation: 3 x 10^7 KITE-585; Dose Escalation: 3 x 10^8 KITE-585; Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585

Cyclophosphamide DRUG

Administered intravenously

Dose Escalation: 1 x 10^8 KITE-585; Dose Escalation: 1 x 10^9 KITE-585; Dose Escalation: 3 x 10^7 KITE-585; Dose Escalation: 3 x 10^8 KITE-585; Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585

Fludarabine DRUG

Administered intravenously

Dose Escalation: 1 x 10^8 KITE-585; Dose Escalation: 1 x 10^9 KITE-585; Dose Escalation: 3 x 10^7 KITE-585; Dose Escalation: 3 x 10^8 KITE-585; Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (9)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 34249462 BACKGROUND

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483(1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose-Escalation and Dose Expansion

Study Record Dates

• First Submitted: October 13, 2017
• First Posted: October 24, 2017
• Study Start: October 20, 2017
• Primary Completion: December 17, 2018
• Study Completion: September 16, 2022
• Last Updated: October 19, 2023
• Results First Posted: May 26, 2020

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)