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

Relapsed/Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03318861
• Other study ID #: KITE-585-501
• Status: Terminated
• Phase: Phase 1
• Start date: October 20, 2017
• Est. completion date: September 16, 2022

Study information

• Verified date: October 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: September 16, 2022
• Est. primary completion date: December 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

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

Drug:
• Cyclophosphamide
Administered intravenously
• Fludarabine
Administered intravenously

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	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)
Secondary	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.	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)
Secondary	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.	From KITE-585 infusion to date of data cutoff (maximum: 17.6 months)
Secondary	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)
Secondary	Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities	Clinically significant laboratory abnormalities were defined as per investigator's discretion.	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)
Secondary	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.	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)
Secondary	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.	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)

External Links

•   Gilead Clinical Trials Website