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

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ClinicalTrials.gov Identifier: NCT04176380
Recruitment Status : Recruiting
First Posted : November 25, 2019
Last Update Posted : January 13, 2021
Sponsor:
Collaborator:
Medical College of Wisconsin
Information provided by (Responsible Party):
Rapa Therapeutics LLC

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.

Condition or disease Intervention/treatment Phase
Relapsed, Refractory Multiple Myeloma Biological: RAPA-201 Autologous T cells Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: No Masking
Primary Purpose: Treatment
Official Title: Phase II Trial of Autologous Rapamycin-Resistant Th1/Tc1 (RAPA-201) Cell Therapy of Relapsed, Refractory Multiple Myeloma
Actual Study Start Date : December 2, 2020
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : October 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Administration of RAPA-201 cells Biological: RAPA-201 Autologous T cells
Autologous rapamycin resistant Th1/Tc1 cells
Other Name: RAPA-201 cells




Primary Outcome Measures :
  1. Overall response rate [ Time Frame: One (1) year after last dose of RAPA-201 cells. ]
    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 :
  1. Effect of therapy on disease control [ Time Frame: One (1) year after the last dose of RAPA-201 cells. ]
    (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).

  2. Effect in Quality of Life [ Time Frame: One (1) year after the last dose of RAPA-201 cells. ]
    To evaluate the effect of therapy on quality of life (QOL) using the FACT-BMT questionnaire.


Other Outcome Measures:
  1. Immune reconstitution [ Time Frame: Screening; Day 1 of every treatment cycle; End of treatment; Day 1 of Months 1, 3, 9 and 12 of Follow-up. ]
    Immune reconstitution of participants receiving RAPA-201 cells will be measured using flow cytometry to obtain the absolute number of circulating CD4+ and CD8+ T cells per microliter of blood.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04176380


Contacts
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Contact: Jennifer Gough Clinical Regulatory Coordinator (617)285-4774 jgough@rapatherapeutics.com

Locations
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United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Binod Dhakal Principal Investigator, MD    414-805-0505    bdhakal@mcw.edu   
Principal Investigator: Binod Dhakal, MD         
Sponsors and Collaborators
Rapa Therapeutics LLC
Medical College of Wisconsin
Investigators
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Study Director: Daniel Fowler, M.D. Rapa Therapeutics LLC
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Responsible Party: Rapa Therapeutics LLC
ClinicalTrials.gov Identifier: NCT04176380    
Other Study ID Numbers: RAPA-201-RRMM
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Rapa Therapeutics LLC:
Multiple Myeloma
Autologous Th1/Tc1 cell Therapy
RAPA-201
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases