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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318861
Recruitment Status : Active, not recruiting
First Posted : October 24, 2017
Results First Posted : May 26, 2020
Last Update Posted : April 25, 2022
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( 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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Genetic: KITE-585 Drug: Cyclophosphamide Drug: Fludarabine Phase 1

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. Subjects 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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose-Escalation and Dose Expansion
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 20, 2017
Actual Primary Completion Date : May 19, 2019
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: 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 autologous anti-B-cell maturation antigen (BCMA) CAR T cells at a dose of 3 x 10^7 3e7 transduced 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
A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Experimental: 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 anti-autologous BCMA CAR T cells at a dose of 1 x 10^8 3e7 transduced 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
A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Experimental: 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 anti-autologous BCMA CAR T cells at a dose of 3 x 10^8 3e7 transduced 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
A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Experimental: 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 anti-autologous BCMA CAR T cells at a dose of 1 x 10^9 3e7 transduced 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
A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Experimental: 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 intravenous infusion of KITE-585 anti-autologous BCMA CAR T cells at a tolerable dose of 3 x 10^7 3e7 transduced 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
A single infusion of KITE-585 autologous anti-BCMA CAR T cells

Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [ Time Frame: 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 :
  1. Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria [ Time Frame: 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.

  2. Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1 [ Time Frame: 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.

  3. Overall Survival (OS) [ Time Frame: 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.

  4. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: From KITE-585 infusion to date of data cutoff (maximum: 17.6 months) ]
  5. Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities [ Time Frame: From KITE-585 infusion to date of data cutoff (maximum: 17.6 months) ]
    Clinically significant laboratory abnormalities were defined as per investigator's discretion.

  6. Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1 [ Time Frame: 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. Analysis was done using KM estimate. Participants not meeting the criteria for PD by the analysis data cutoff date were censored at their last evaluable disease assessment date before any other anti-cancer therapies including stem cell transplant.

  7. Time to Next Treatment (TTNT) [ Time Frame: 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. Analysis was done using KM estimate. Participants with no new anti-cancer therapy and alive by the time of data cutoff were censored at the last date known to be alive or cutoff date, whichever is earlier.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318861


Locations
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United States, California
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Kite, A Gilead Company
Investigators
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Study Director: Kite Study Director Kite, A Gilead Company
  Study Documents (Full-Text)

Documents provided by Gilead Sciences ( Kite, A Gilead Company ):
Study Protocol  [PDF] September 11, 2017
Statistical Analysis Plan  [PDF] March 26, 2019

Additional Information:
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Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov Identifier: NCT03318861    
Other Study ID Numbers: KITE-585-501
First Posted: October 24, 2017    Key Record Dates
Results First Posted: May 26, 2020
Last Update Posted: April 25, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists