RAPA-201 T Cell Therapy for Relapsed, Refractory Multiple Myeloma

NCT04176380 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: RAPA-201-RRMM
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

RAPA-201-RRMM is an open-label, single-arm, non-randomized multicenter phase II study of RAPA-201 autologous T cells in adults with relapsed, refractory multiple myeloma who have received at least three (3) prior lines.

Conditions

Relapsed, Refractory Multiple Myeloma

Keywords

Multiple Myeloma; Autologous Th1/Tc1 cell Therapy; RAPA-201

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  To determine the overall response rate, as evaluated by IMWG criteria, in patients with relapse, refractory multiple myeloma (RRMM) treated with autologous RAPA-201 cells and a pentostatin-cyclophosphamide (PC) host conditioning regimen.

  One (1) year after last dose of RAPA-201 cells.

Secondary Outcomes (2)

• Effect of therapy on disease control

  One (1) year after the last dose of RAPA-201 cells.

• Effect in Quality of Life

  One (1) year after the last dose of RAPA-201 cells.

Other Outcomes (1)

• Immune reconstitution

  Screening; Day 1 of every treatment cycle; End of treatment; Day 1 of Months 1, 3, 9 and 12 of Follow-up.

Study Arms (1)

Administration of RAPA-201 cells

EXPERIMENTAL

Biological: RAPA-201 Autologous T cells

Interventions

RAPA-201 Autologous T cells BIOLOGICAL

Autologous rapamycin resistant Th1/Tc1 cells

Also known as: RAPA-201 cells

Administration of RAPA-201 cells

Eligibility Criteria

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

You may qualify if:

• Male or female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Diagnosis of relapsed, refractory multiple myeloma.
• Exposure to at least three different prior lines of therapy including exposure to at least two proteosome inhibitors (e.g. bortezomib), and at least two immunomodulatory drugs (e.g. lenalidomide) and at least one anti-CD38 monoclonal antibody agent (e.g. daratumumab). To qualify as a prior line of therapy, ≥ 2 cycles of therapy must be administered unless the disease is refractory, or the regimen is not tolerated. Documentation of a prior line of therapy must include at least one of the following three items: \[1\] medical records detailing prior treatment, best response to treatment, and date of progression; \[2\] myeloma markers (SPEP, UPEP, Immunoglobulin, FLC) at time of treatment and progression; or, \[3\] documentation by investigator/treating physician to be included in patient's medical and research record (for example, note in electronic medical record), indicating prior treatment, best response to treatment, and data of progression.
• Refractory status to ≥ one proteasome inhibitor AND ≥ one immunomodulatory drug. Refractory disease is defined as \<25% reduction in M-protein/free light chain difference (involved vs. uninvolved) or disease progression during treatment or ≤ 60 days after treatment cessation. Patient may or may not be refractory to anti-CD38 therapy.
• Presence of secretory myeloma/measurable disease, as defined by ONE of the following:
• Serum M-protein (SPEP) ≥ 0.5 mg/dL or
• Urine M-protein (UPEP) ≥ 200 mg/24 hours; or
• Light chain MM: Serum free light chain (FLC) assay ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa/lambda FLC ratio.
• Must have a potential source of autologous T cells potentially sufficient to manufacture RAPA-201 cells, as defined by a circulating CD3+ T cell count ≥ 300 cells/µL.
• Prior to apheresis, patients must be ≥ 14 calendar days from last myeloma therapy, major surgery, radiation therapy and participation in investigational trials.
• Patients must have recovered from clinical toxicities (resolution of CTCAE toxicity to a value of ≤ 2).
• Left ventricular ejection fraction (LVEF) by MUGA or 2-D echocardiogram within institution normal limits, with an LVEF level of ≥ 40%.
• Serum creatinine ≤ to 2.5 mg/dL.
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ to 3 x upper limit of normal (ULN).

You may not qualify if:

• Prior allogeneic stem cell transplantation.
• Current plasma cell leukemia (circulating myeloma \> 20% of leukocytes).
• Other active malignancy (except for non-melanoma skin cancer).
• Non-secretory multiple myeloma (difficult to assess by IMWG criteria).
• Evidence of systemic AL Amyloidosis involving any vital organ. Incidental histologic demonstration of amyloid deposition in marrow/within plasmacytoma is not considered organ involvement.
• Life expectancy \<4 months.
• Patients seropositive for HIV, hepatitis B, or hepatitis C.
• Uncontrolled hypertension.
• History of cerebrovascular accident within 6 months prior to enrollment.
• Myocardial infarction within 6 months prior to enrollment.
• NYHA class III/IV congestive heart failure.
• Uncontrolled angina/ischemic heart disease.
• Subjects with known central nervous system disease.
• Pregnant or breastfeeding patients.
• Patients of childbearing age, or males who have a partner of childbearing potential, who are unwilling to practice contraception.

Sponsors & Collaborators

• Rapa Therapeutics LLC: lead
• Medical College of Wisconsin: collaborator

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Dhakal B, Hari P, Chhabra S, Szabo A, Lum LG, Glass DD, Park JH, Donato M, Siegel DS, Felizardo TC, Fowler DH. Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma. J Immunother Cancer. 2025 Jan 28;13(1):e010649. doi: 10.1136/jitc-2024-010649.

  PMID: 39875173 DERIVED

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; 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

Study Officials

• Daniel Fowler, M.D.

  Rapa Therapeutics LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No Masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 25, 2019
• Study Start: December 2, 2020
• Primary Completion: January 30, 2023
• Study Completion: June 6, 2023
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)