TriPRIL CAR T Cells in Multiple Myeloma

NCT05020444 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-518
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This research study involves the study of TriPRIL CAR T Cells for treating people with relapsed or refractory multiple myeloma and to understand the side effects when treated with TriPRIL CAR T Cells. This research study involves the study drugs:.

• TriPRIL CAR T Cells
• Fludarabine and Cyclophosphamide: Standardly used chemotherapy drugs as part of lymphodepleting process

Conditions

Multiple Myeloma; Multiple Myeloma in Relapse; Refractory Multiple Myeloma

Keywords

Multiple Myeloma; Multiple Myeloma in Relapse; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Study-related adverse events (AEs) will be listed and tabulated by type and study cohort. The rate of AEs in all infused patients, both within study cohorts and overall, will be calculated and reported with exact 95% confidence intervals. A separate safety analysis will report similar information within patients infused at the target dose of 1x108 or 3x108 TriPRIL CAR T cells.

  Week 24 post dosing, and every three months until two years.

• Incidence of Dose Limiting Toxicity (DLT)

  Dose-limiting toxicities will be listed and tabulated by type and study cohort.

  Week 24 post dosing, and every three months until two years.

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  1 month, 6 months, 12 months, and 24 after CAR T cell treatment.

• Overall Survival (OS)

  1 month, 6 months, 12 months and 24 months after CAR T cell treatment.

• Progression Free Survival (PFS)

  1 month, 6 months, 12 months and 24 months after CAR T cell treatment.

Study Arms (2)

TriPRIL CAR T Cells-Dose Escalation

EXPERIMENTAL

Prior to receiving TriPRIL CAR T Cells, participants will undergo two preparatory processes: * Leukapheresis: White blood cells will be collected and manufacture TriPRIL CAR T cells at a GMP manufacturing facility. * Lymphodepletion: On days, -5, -4. -3 participants will receive 3 days of chemotherapy to decrease the number of lymphocytes TriPRIL CAR T Cells will be administered intravenously on day 0 using a 3+3 dose escalation design

Drug: TriPRIL CAR T Cells; Drug: Cyclophosphamide; Drug: Fludarabine

TriPRIL CAR T Cells-Dose Expansion

EXPERIMENTAL

Prior to receiving TriPRIL CAR T Cells, participants will undergo two preparatory processes: * Leukapheresis: White blood cells will be collected and manufacture TriPRIL CAR T cells at a GMP manufacturing facility. * Lymphodepletion: On days, -5, -4. -3 participants will receive 3 days of chemotherapy to decrease the number of lymphocytes TriPRIL CAR T Cells will be administered intravenously on day 0 using the respective dose (at or below the Maximum Tolerated Dose-MTD), as determined during the dose escalation part.

Drug: TriPRIL CAR T Cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

TriPRIL CAR T Cells DRUG

Intravenous infusion

TriPRIL CAR T Cells-Dose Escalation; TriPRIL CAR T Cells-Dose Expansion

Cyclophosphamide DRUG

Intravenous infusion

Also known as: Cytoxan, Neosar

TriPRIL CAR T Cells-Dose Escalation; TriPRIL CAR T Cells-Dose Expansion

Fludarabine DRUG

Intravenous infusion

Also known as: Fludara

TriPRIL CAR T Cells-Dose Escalation; TriPRIL CAR T Cells-Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥18 years at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of greater than 12 weeks
• Histologically or cytologically confirmed diagnosis of relapsed/refractory multiple myeloma. Documented measurable disease includes at least one or more of the following criteria:
• Serum M-protein ≥1.0 g/dL
• Urine M-protein ≥200 mg/24 hours
• Involved serum free light chain ≥100 mg/L with abnormal κ/λ ratio
• Bone marrow plasma cells ≥30%
• Relapsed/refractory multiple myeloma with at least 3 prior regimens of systemic therapy including proteasome inhibitor, IMiDs and anti-CD38 antibody; or has "triple-refractory" disease following treatment with proteasome inhibitor, IMiD and anti-CD38 antibody, as part of the same or different regimens.
• Note: IMWG criteria defines refractory disease as disease progression on or within 60 days of receiving a therapy Note: Induction treatment with or without hematopoietic stem cell transplant and with or without maintenance is considered a single regimen.
• Adequate organ and marrow function as defined below:
• O2 saturation ≥92% on room air while awake
• LVEF ≥40% by ECHO or MUGA scan
• ANC ≥1.0k/μl, PLT ≥50k/μl, (NOTE: Platelet transfusion not allowed within 7 days; growth factor neupogen not allowed within 7 days, neulasta within 14 days)

You may not qualify if:

• Treatment with any of the following therapies as specified below:
• Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis unless discussed with the medical monitor
• Receiving high-dose (e.g., \>10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis
• Autologous stem cell transplantation within 3 months prior to leukapheresis
• Any prior allogeneic stem cell transplantation
• Other CAR-T cell therapy within 6 months of leukapheresis
• Plasma cell leukemia or history of plasma cell leukemia
• No Bispecific T cell engagers withing 6 months of apheresis
• No bendamustine within 6 months of apheresis
• Patients with solitary plasmacytomas without evidence of other measurable disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CAR- T cells
• Contraindication to the protocol-specified doses of fludarabine or cyclophosphamide
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of ≤ G2 alopecia and grade ≤2 sensory neuropathy.
• Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, e.g., related to disease)
• Symptomatic congestive heart failure

Sponsors & Collaborators

• Marcela V. Maus, M.D.,Ph.D.: lead

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Matthew J Frigault, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew J Frigault, MD

CONTACT

(617) 643-6175; MFRIGAULT@partners.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 25, 2021
• Study Start: October 5, 2021
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: February 23, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)