Clinical Trials /

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

NCT04176380

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: RAPA-201 T Cell Therapy for Relapsed, Refractory Multiple Myeloma
  • Official Title: Phase II Trial of Autologous Rapamycin-Resistant Th1/Tc1 (RAPA-201) Cell Therapy of Relapsed, Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: RAPA-201-RRMM
  • NCT ID: NCT04176380

Conditions

  • Relapsed, Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
RAPA-201 Autologous T cellsRAPA-201 cellsAdministration of RAPA-201 cells

Purpose

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.

Detailed Description

      This is an open-label, single-arm, non-randomized multicenter Phase 2 study evaluating
      RAPA-201 cells in subjects with relapsed, refractory multiple myeloma.

      After a subject consents to the study, an apheresis procedure will be performed to collect
      cells to manufacture the investigational product, RAPA-201 cells. During Cycle 1, subjects
      will receive pentostatin and low-dose, dose-adjusted Cyclophosphamide (PC regimen), but will
      not receive RAPA-201 cells. During Cycles 2 and beyond, Subjects will receive a conditioning
      regimen consisting of the PC regimen followed by the RAPA-201 cell infusions.

      Subjects will receive at minimum five cycles of treatment. If a subject has stable disease,
      they will receive an additional four cycles of PC regimen+RAPA-201 cells.

      All subjects who complete the active treatment portion of the study, prematurely terminate
      the study, or subjects who discontinue active treatment due to a toxicity attributable or
      related to the study drug will complete the follow-up portion of the study (approximately one
      year).

      Patients who experience progressive disease will be taken off study.
    

Trial Arms

NameTypeDescriptionInterventions
Administration of RAPA-201 cellsExperimental
  • RAPA-201 Autologous T cells

Eligibility Criteria

        Inclusion Criteria:

          -  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) 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. 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.

          -  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:

               1. Serum M-protein (SPEP) ≥ 0.5 mg/dL or

               2. Urine M-protein (UPEP) ≥ 200 mg/24 hours

               3. 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 ≥ 400
             cells/µL.

          -  Patients must be ≥ two weeks 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).

          -  Ejection fraction (EF) by MUGA or 2-D echocardiogram within institution normal limits,
             with an EF 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).

          -  Absolute neutrophil count (ANC) of ≥ 1000 cells/µL (independent of growth factor
             support for at least 7 days prior to screening).

          -  Platelet count of ≥ 50,000 cells/µL, with value obtained (independent of growth factor
             support or transfusion support for at least 7 days prior to screening).

          -  Hemoglobin count ≥ 8 grams/µL (independent of growth factor support or transfusion
             support for at least 7 days prior to screening).

          -  Bilirubin ≤ 1.5 (except if due to Gilbert's disease).

          -  Corrected DLCO ≥ 50% (Pulmonary Function Test).

          -  No history of abnormal bleeding tendency.

          -  Voluntary written consent must be given before performance of any study related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the patient at any time without prejudice to future medical care.

        Exclusion Criteria:

          -  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 of 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.

          -  Patients may be excluded at PI discretion or if it is deemed that allowing
             participation would represent an unacceptable medical or psychiatric risk.

          -  Subjects should not receive any prior systemic therapy within 14 days of the protocol
             required apheresis procedure.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:One (1) year after last dose of RAPA-201 cells.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Effect of therapy on disease control
Time Frame:One (1) year after the last dose of RAPA-201 cells.
Safety Issue:
Description:(1) To determine the effect of therapy on multiple myeloma disease control, including duration of response (DOR; time from initial tumor response to disease progression).
Measure:Effect in Quality of Life
Time Frame:One (1) year after the last dose of RAPA-201 cells.
Safety Issue:
Description:To evaluate the effect of therapy on quality of life (QOL) using the FACT-BMT questionnaire.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Rapa Therapeutics LLC

Trial Keywords

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

Last Updated

November 21, 2019