CAR- PRISM (PRecision Intervention Smoldering Myeloma)

NCT05767359 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-546
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to test if ciltacabtagene autoleucel (cilta-cel) is safe and effective in treating participants with high-risk, smoldering myeloma. The names of the treatment interventions used in this study are:

• Cilta-cel (or chimeric antigen receptor T cells)
• Cyclophosphamide (a lymphodepleting chemotherapy)
• Fludarabine (a lymphodepleting chemotherapy)

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Keywords

Multiple Myeloma; Smoldering Multiple Myeloma; Chemotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose Limiting Toxicities (DLT)

  Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration. Dose-Limiting Toxicities (DLTs) will be defined as follows: * Grade 4 non-hematologic toxicity of any duration including Grade 4 CRS and ICANS * Grade 3 CRS that does not improve to a grade 2 or less in 72 hours following adequate therapy. * Grade 3 neurological toxicity of any duration * Grade 3 toxicity of any duration involving vital organs (cardiac, pulmonary). Exceptions can be made if associated with CRS. * Other Grade 3 toxicity lasting \> 72 hours. Exceptions may be made for Grade 3 abnormal hepatic or renal function tests that improve to grade 2 or less within 7 days. * Grade 3 hypersensitivity reaction that is not reversible to Grade 2 or less within 24 hours * Grade 4 neutropenia or thrombocytopenia lasting more than 28 days

  24 months

• Nature of Dose Limiting Toxicities (DLT)

  Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration. Dose-Limiting Toxicities (DLTs) will be defined as follows: * Grade 4 non-hematologic toxicity of any duration including Grade 4 CRS and ICANS * Grade 3 CRS that does not improve to a grade 2 or less in 72 hours following adequate therapy. * Grade 3 neurological toxicity of any duration * Grade 3 toxicity of any duration involving vital organs (cardiac, pulmonary). Exceptions can be made if associated with CRS. * Other Grade 3 toxicity lasting \> 72 hours. Exceptions may be made for Grade 3 abnormal hepatic or renal function tests that improve to grade 2 or less within 7 days. * Grade 3 hypersensitivity reaction that is not reversible to Grade 2 or less within 24 hours * Grade 4 neutropenia or thrombocytopenia lasting more than 28 days

  24 months

• Incidence of Adverse Events (AEs)

  Adverse events with onset or worsening on or after date of first dose of study treatment. AEs with onset or worsening on or after date of first dose of study treatment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to AE. SAE is any untoward medical occurrence that results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

  24 months

Secondary Outcomes (9)

• Manufacture Success Rate (Feasibility)

  24 months

• Overall Response Rate (ORR)

  6 months

• Complete Response Rate

  3 months

• Duration of Response

  12 months from infusion of cellular product

• Cmax of BCMA CAR-T Cells

  24 months

Study Arms (2)

Safety Run-In

EXPERIMENTAL

Participants will be enrolled into each of the 2 safety run-in phases in a standard 3 + 3 design. \- Participants will undergo study procedures as outlined: * Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site * Stem cell collection on-site post-apheresis per standard care. * Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days. * Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion. * Follow-up for 3 years post-treatment and up to 15 years.

Drug: Ciltacabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate

Cilta-Cel Dose Expansion Cohort

EXPERIMENTAL

Expansion cohort of 14 participants will be enrolled after safety run-in phases, and participants will undergo study procedures as outlined: * Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site * Stem cell collection on-site post-apheresis per standard care. * Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days. * Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion. * Follow-up for 3 years post-treatment and up to 15 years.

Drug: Ciltacabtagene Autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate

Interventions

Ciltacabtagene Autoleucel DRUG

Genetically modified autologous T-cell immunotherapy, via intravenous infusion per protocol.

Also known as: Cilta-cel, JNJ-68284528, LCAR-B38M

Cilta-Cel Dose Expansion Cohort; Safety Run-In

Cyclophosphamide DRUG

Lymphodepleting conditioning regimen, nitrogen mustard-derivative, via intravenous infusion per standard care.

Also known as: Cytoxan

Cilta-Cel Dose Expansion Cohort; Safety Run-In

Fludarabine Phosphate DRUG

Lymphodepleting conditioning regimen, synthetic purine nucleoside, via intravenous infusion per standard care.

Also known as: Fludarabine, Fludara

Cilta-Cel Dose Expansion Cohort; Safety Run-In

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years.
• High-risk SMM with ≤40% plasma cells in the bone marrow and with high-risk criteria defined as having 1 of the following 2 criteria:
• High-risk per "20-2-20" Criteria defined as presence of any two of the following:
• Serum M-protein ≥ 2 gm/dL
• Involved to uninvolved free light chain (FLC) ratio≥ 20
• Bone marrow PC% ≥ 20% to \<40%.
• OR total score of 9 using the following scoring system:
• FLC Ratio
• \>10-25 = 2
• \>25-40 = 3
• \> 40 = 5
• Serum M-protein (g/dL)
• \>1.5-3 = 3
• \>3 = 4
• BMPC%

You may not qualify if:

• Prior SMM directed therapy.
• Symptomatic Multiple Myeloma or any evidence of CRAB criteria, including presence of myeloma defining events (MDE). Any prior therapy for active Myeloma should also be excluded. Bisphosphonates are not excluded.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, inflammatory disorders, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Plans to father a child while enrolled in this study or within 1 year after receiving the last dose of study drug.
• Pregnant or breast-feeding or planning to become pregnant while enrolled in this study or within 1 year after receiving the last dose of study drug.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or SARS-CoV-2 (COVID-19).
• Participants who are seropositive because of hepatitis B virus vaccine are eligible.
• Participants who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Participants who are positive for HIV1 or 2 infections, with undetectable viral load and on stable antiretrovirals, will not be excluded.
• Participants with past HCV infection that have now cleared will not be excluded.
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to Investigator's Brochure and appropriate package inserts).
• Prior or concurrent exposure to any of the following:
• Teclistamab, Belantamab, or any anti-BCMA therapy

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine phosphate; 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; Precancerous Conditions; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

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

Study Officials

• Irene Ghobrial, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 14, 2023
• Study Start: April 19, 2023
• Primary Completion: December 15, 2025
• Study Completion (Estimated): January 15, 2040
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)