Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05577000
Other study ID # 22702
Secondary ID NCI-2022-08957
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date October 18, 2021
Est. completion date October 1, 2043

Study information

Verified date May 2024
Source University of California, San Francisco
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an open-label study to determine the safety of anti-B-cell maturation antigen (BCMA) Chimeric antigen receptor T-cell (CAR T) therapy in participants with Relapsed or Refractory Multiple Myeloma (RRMM).


Description:

PRIMARY OBJECTIVE: 1. To evaluate the safety of administering chimeric antigen receptor (CAR)-T cells targeting BCMA to participants with RRMM (Dose Escalation). 2. To determine the maximum tolerated dose (MTD) for anti-BCMA CAR-T cells (Dose Escalation). 3. Determine whether administering chimeric antigen receptor T cells targeting BCMA to participants with RRMM increases the overall response rate (ORR) in RRMM compared with historical data for non-CAR agents per International Myeloma Working Group (IMWG) response criteria (Dose Expansion). SECONDARY OBJECTIVES: Dose Expansion Only: 1. To describe the efficacy of CAR-T cells targeting BCMA in participants with RRMM. 2. To evaluate the feasibility of manufacturing anti-BCMA CAR-T cells locally and ability to produce adequate quantities of vector positive T-cells. 3. To evaluate the safety and toxicity of CAR-T cells targeting BCMA to participants with RRMM OUTLINE: Participants will be enrolled sequentially to each dose level dependent on analysis of dose-limiting toxicities at the previous dose level. A dose expansion will occur at the maximum tolerated dose (MTD). Participants will undergo apheresis with collection of autologous peripheral blood mononuclear cells that will be used to generate CAR-T cells. After successful generation of the anti-BCMA CAR-T cells drug product (DP), participants will undergo lymphodepleting chemotherapy with fludarabine (and cyclophosphamide. Participants will undergo an additional evaluation of eligibility on Day -1 or 1 prior to infusion of anti-BCMA CAR-T cell product. A single infusion of anti-BCMA CAR-T cells at the starting dose will be given on Day 1. Following treatment with DP, participants will be followed up at 12 months and annually for up to 15 years.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 5
Est. completion date October 1, 2043
Est. primary completion date October 31, 2028
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Eligibility for enrollment: Inclusion Criteria: 1. Voluntarily sign informed consent form 2. >=18 years of age at the time of signing informed consent 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (PI; e.g., bortezomib or carfilzomib) immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), and anti-CD38 antibody therapy 5. Participants must have measurable disease, including at least one of the criteria below: 1. Serum M-protein greater or equal to 0.5 g/dL. 2. Urine M-protein greater or equal to 200 mg/24 h. 3. Serum free light chain (FLC) assay: involved FLC level of >= 100 mg/L. 6. Adequate organ function, defined as: 1. Hemoglobulin >8 gm/dl (transfusions allowed). 2. Platelets >50,000/microliter (uL) (in the absence of platelet transfusion within 7 days of apheresis, but transfusion permitted prior to lymphodepleting chemotherapy). 3. Absolute neutrophil count (ANC) > 1000/uL in the absence of growth factor support (filgrastim within 7 days or pegfilgrastim within 14 days of apheresis, but growth factor permitted prior to lymphodepleting chemotherapy). 4. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x institutional upper limit of normal (ULN). 5. Total bilirubin =< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome. 6. Serum creatinine clearance (CrCl) >= 45 mL/min using Cockcroft-Gault formula. 7. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) >= 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA). 7. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-BCMA CAR-T cells. 8. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method. Exclusion Criteria: 1. Autologous transplant within 6 weeks of planned CAR-T cell infusion. 2. Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast). Any fully treated malignancies or indolent, clinically insignificant malignancies can be discussed among the study team to determine eligibility. 3. HIV seropositivity. 4. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded). 5. Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pulmonary abnormalities, or psychiatric illness/social situations that would limit compliance with study requirements. 6. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test. 7. Patients with currently symptomatic central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia, and Parkinson's disease. 8. History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months. Eligibility for Infusion of Investigational Product: Includes the inclusion/exclusion criteria required for enrollment with the following exceptions and additions. Inclusion criteria exceptions: 1. Hematologic function parameters will not be included as a pre-infusion eligibility criterion (because lymphodepletive chemotherapy is expected to cause pancytopenia). 2. Laboratory result abnormalities that are considered not clinically significant by the principal investigator, AND are not the result of a demonstrated active infection or an active central nervous system condition. Exclusion criteria additions: 1. Use of anti-multiple myeloma therapy, including systemic corticosteroids within 14 days prior to lymphodepletive chemotherapy. 2. Neurologic symptoms suggestive of an active central nervous system condition.

Study Design


Intervention

Biological:
Manufactured Anti-BCMA CAR-T cells
Given IV
Drug:
Fludarabine
Given IV
Cyclophosphamide
Given IV

Locations

Country Name City State
United States University of California, San Francisco San Francisco California

Sponsors (4)

Lead Sponsor Collaborator
Thomas Martin, MD Actavis Inc., Eugia Pharma Specialities Limited, University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of participants with treatment-emergent adverse events (AE) (Dose Escalation) Proportion of participants with treatment-emergent adverse events of CAR-T as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, revised cytokine release syndromeCRS grading criteria (for CRS), and American Society of Transplantation and Cellular Therapy (ASTCT) Immune Effector Cell Associated Neurotoxicity (ICANS) Consensus Grading for Adults (for neurotoxicity). From initiation of study treatment (day 1) to 29 days following CAR-T infusion
Primary Proportion of participants who experience a dose-limiting toxicity (DLT) (Dose Escalation) The DLT evaluable analysis set includes all participants in the dose-finding part of the study who have received the anti-BCMA CAR-T cell product, and who have either experienced a DLT or were followed for the full DLT evaluation period (within 28 days following infusion of CAR-T cells targeting BCMA). The MTD is defined as the dose level immediately below that in which >=2/6 participants experience a DLT and will be used to determine the recommended Phase 2 dose for future studies. From initiation of study treatment (day 1) to 29 days following CAR-T infusion
Primary Overall Response Rate (ORR) Overall response rate includes participants with a demonstrated Stringent Complete Response (sCR), Complete Response (CR), Partial Response (PR), or Very Good Partial Response (VGPR) per International Myeloma Working Group (IMWG) criteria reported as proportion with 90% binomial confidence interval for the expansion cohort including the patients on MTD in the dose escalation cohort Up to 12 months following CAR- T infusion
Secondary Duration of response This is measured, only in responders, from the documented beginning of response (sCR, CR, PR or VGPR) to the time of progression per IMWG criteria for the expansion cohort including the patients on MTD in the dose escalation cohort Up to 12 months following CAR- T infusion
Secondary Progression-free Survival (PFS) PFS is defined as the rate of survival from the the time from entry onto study until MM progression by IMWG criteria, or death from any cause for the expansion cohort including the patients on MTD in the dose escalation cohort. Up to 12 months following CAR- T infusion
Secondary Overall Survival Overall Survival is defined as the time from entry onto study until multiple myeloma progression or death from any cause. and will be be analyzed by Kaplan-Meier method for the expansion cohort including the patients on MTD in the dose escalation cohort. Up to 15 years
Secondary Proportion of participants for whom BCMA CAR T-cell therapy is manufactured successfully Participants who have anti-BCMA CAR T-cells successfully manufactured locally and are able to produce adequate quantities of vector positive T-cells which meet pre-specified release criteria. From initiation of CAR T-cell manufacturing to end of infusion, up to 21 days
Secondary Proportion of participants who complete study treatment Participants who have anti-BCMA CAR T-cells successfully manufactured locally and are able to produce adequate quantities of vector positive T-cells which meet pre-specified release criteria which are then infused with the drug product. From initiation of CAR T-cell manufacturing to end of infusion, up to 21 days
Secondary Proportion of participants with treatment-emergent adverse events (AE) (Dose Expansion) Proportion of participants with treatment-emergent adverse events of CAR-T as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, revised cytokine release syndrome CRS grading criteria (for CRS), and American Society of Transplantation and Cellular Therapy (ASTCT) Immune Effector Cell Associated Neurotoxicity (ICANS) Consensus Grading for Adults (for neurotoxicity). From initiation of CAR T-cell manufacturing to end of first follow-up, approximately 13 months
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04083534 - First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) Phase 1/Phase 2
Active, not recruiting NCT02101944 - Wild-Type Reovirus in Combination With Carfilzomib and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT01775553 - Study of High Dose Carfilzomib in Multiple Myeloma Patients Who Have Progressed On Standard Dose Carfilzomib Phase 2
Terminated NCT02020941 - Carfilzomib in Treating Patients With Multiple Myeloma in First Relapse or Refractory to First-Line Therapy Phase 2
Completed NCT01212952 - Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 1/Phase 2
Terminated NCT01078441 - Bortezomib, Liposomal Doxorubicin Hydrochloride, Dexamethasone, and Cyclophosphamide in Treating Patients With Multiple Myeloma That Relapsed After Autologous Stem Cell Transplant Phase 2
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT00514137 - Sunitinib in Treating Patients With Relapsed Multiple Myeloma Phase 2
Completed NCT00306813 - Evaluation of Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma Phase 1/Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00047203 - Flavopiridol in Treating Patients With Relapsed or Refractory Multiple Myeloma Phase 2
Active, not recruiting NCT03731832 - Pomalidomide, Ixazomib, and Dexamethasone With or Without Intensification by Cyclophosphamide in Relapsed or Refractory Multiple Myeloma Phase 2
Completed NCT00003196 - Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma N/A
Recruiting NCT03601624 - Pomalidomide/Cyclophosphamide/Dexamethasone in Relapse Refractory Myeloma: Safety Profile in Mexicans Phase 2
Terminated NCT01954784 - Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma Phase 1
Recruiting NCT05020444 - TriPRIL CAR T Cells in Multiple Myeloma Phase 1
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1
Recruiting NCT04302324 - A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab Phase 2
Recruiting NCT06119685 - IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers Phase 1/Phase 2
Completed NCT00118170 - Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function Phase 1