Back to results

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

Primary Purpose

Relapsed/Refractory Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

KITE-585

Cyclophosphamide

Fludarabine

About this trial

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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 Exclusion Criteria:

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Dose Escalation: 3 x 10^7 KITE-585

Dose Escalation: 1 x 10^8 KITE-585

Dose Escalation: 3 x 10^8 KITE-585

Dose Escalation: 1 x 10^9 KITE-585

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

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria

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.

Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1

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)

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 Treatment-Emergent Adverse Events

Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities

Clinically significant laboratory abnormalities were defined as per investigator's discretion.

Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1

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.

Time to Next Treatment (TTNT)

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.

Full Information

NCT ID

NCT03318861

First Posted

October 13, 2017

Last Updated

October 17, 2023

Sponsor

Kite, A Gilead Company

1. Study Identification

Unique Protocol Identification Number

NCT03318861

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Terminated

Why Stopped

The study was terminated due to lack of efficacy

Study Start Date

October 20, 2017 (Actual)

Primary Completion Date

December 17, 2018 (Actual)

Study Completion Date

September 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Kite, A Gilead Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed/Refractory Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Dose-Escalation and Dose Expansion

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Escalation: 3 x 10^7 KITE-585

Arm Type

Experimental

Arm Description

Arm Title

Dose Escalation: 1 x 10^8 KITE-585

Arm Type

Experimental

Arm Description

Arm Title

Dose Escalation: 3 x 10^8 KITE-585

Arm Type

Experimental

Arm Description

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.

Arm Title

Dose Escalation: 1 x 10^9 KITE-585

Arm Type

Experimental

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Genetic

Intervention Name(s)

KITE-585

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Administered intravenously

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

Administered intravenously

Primary Outcome Measure Information:

Title

Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria

Description

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)

Title

Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1

Description

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)

Title

Overall Survival (OS)

Description

Time Frame

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

Title

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Time Frame

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)

Title

Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities

Description

Clinically significant laboratory abnormalities were defined as per investigator's discretion.

Time Frame

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)

Title

Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1

Description

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)

Title

Time to Next Treatment (TTNT)

Description

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.

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kite Study Director

Organizational Affiliation

Kite, A Gilead Company

Official's Role

Study Director

Facility Information:

Facility Name

David Geffen School of Medicine at UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

H. Lee Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Winship Cancer Institute, Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

University of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

The University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34249462

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.

Results Reference

background

Links:

URL

https://www.gileadclinicaltrials.com/study/?id=KITE-585-501

Description

Gilead Clinical Trials Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs

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

Relapsed/Refractory Multiple Myeloma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial