Clinical Trials /

MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma

NCT04555551

Description:

This study will test the safety of the study treatment, MCARH109, at different doses, to see which dose is safest in people, and to look for any good and bad effects of this treatment. The study treatment could stop the growth of the cancer, but it could also cause side effects.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
  • Official Title: Phase I Trial of G Protein-coupled Receptor Class C Group 5 Member D (GPRC5D) Targeted MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 18-367
  • NCT ID: NCT04555551

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Infusion of MCARH109 T cellsTargeted MCARH109 CAR Modified T cells

Purpose

This study will test the safety of the study treatment, MCARH109, at different doses, to see which dose is safest in people, and to look for any good and bad effects of this treatment. The study treatment could stop the growth of the cancer, but it could also cause side effects.

Trial Arms

NameTypeDescriptionInterventions
Targeted MCARH109 CAR Modified T cellsExperimentalPatients will undergo leukapheresis of peripheral blood for further T cell enrichment; activation and genetic modification using a lentiviral vector encoding a GPRC5D targeted CAR (MCARH109). These T cells will be expanded and after the appropriate number of cells is generated, the modified T cells may be infused fresh or frozen for later use according to standard operation procedures. These modified T cell infusions will be administered 2-7 days following completion of conditioning chemotherapy.
  • Infusion of MCARH109 T cells

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed MM by MSKCC pathologist.

          -  Age ≥ 18 years of age

          -  Diagnosis of relapsed or refractory multiple myeloma with at least 3 prior lines of
             therapy.

          -  Refractory myeloma is defined as disease that progresses while on therapy or within 60
             days after the last therapy. Relapsed myeloma id defined as previously treated myeloma
             with initial response and subsequent progression (per IMWG criteria) not meeting
             criteria for refractory disease.

          -  At least 3 prior lines of therapy; Prior therapy should include all of the following-

               -  A proteasome inhibitor (e.g. bortezomib, carfilzomib, ixazomib)

               -  An immunomodulatory drug (e.g. thalidomide, lenalidomide, pomalidomide)

               -  A CD38 monoclonal antibody (e.g. daratumumab)

               -  High dose chemotherapy with autologous stem cell support (ASCT) Subjects who are
                  not candidates to receive one or more of the above treatments are eligible for
                  the trial

          -  ECOG performance status of 0 or 1

          -  HGB ≥ 8 g/dl, ANC≥ 1,000/mm3, Platelet≥ 50,000/mm3 without red cell transfusion for 21
             days, platelet transfusion for 7 days and or growth factor support (Neupogen or
             Neulasta) for at least 14 days prior to initial screening (screening A). HGB ≥ 8 g/dl,
             ANC≥ 1,000/mm3, Platelet≥ 20,000/mm3 prior to pre-treatment screening (screening B).
             Patients are allowed to receive transfusion support prior to the pre-treatment
             screening but no growth factor support (Neupogen or Neulasta) for 7 days prior to
             pre-treatment screening.

          -  Measurable disease defined as meeting at least one of the criteria below-

               -  Serum M protein ≥ 0.5 g/dL

               -  Involved serum free light chain ≥10 mg/dL with an abnormal free light chain ratio

               -  Urine M-protein ≥ 200 mg/24 hours

               -  Measurable plasmacytomas seen on imaging (≥ 1 lesion that has a single diameter ≥
                  2 cm) If this is the primary marker of measurable disease, patients will need a
                  biopsy at the pre-treatment screening (screening B).

               -  Bone marrow plasma cells ≥ 30% as determined by CD138 immunohistochemistry
                  staining

          -  Serum creatinine ≤ 1.5mg/dL or a measured creatinine clearance ≥ 50 mL/min (using
             24-hour urine collection)

          -  ALT and AST ≤ 3 X ULN and total bilirubin ≤ 2 mg/dL (or < 3 mg/dL for individuals with
             Gilbert's syndrome)

          -  PT and PTT ≤ 1.5 X ULN

          -  Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse
             oximetry

          -  Adequate cardiac function, defined as LVEF ≥ 40% by echocardiogram performed within 4
             weeks of initial screening

          -  For patients with prior ASCT, at least 100 days since ASCT at the time of initial
             screening

        Exclusion Criteria:

          -  Pregnant or lactating women. Women and men of childbearing age should use highly
             effective contraception while on this study and continue for 1 year after all
             treatment is finished.

          -  Patients with following cardiac conditions will be excluded:

               -  New York Heart Association (NYHA) stage III or IV congestive heart failure

               -  Myocardial infarction ≤6 months prior to enrollment

               -  History of clinically significant ventricular arrhythmia or unexplained syncope,
                  not believed to be vasovagal in nature or due to dehydration

               -  History of severe non-ischemic cardiomyopathy

          -  Patients with HIV or active hepatitis B or hepatitis C infection are ineligible.

          -  Current diagnosis of primary and secondary plasma cell leukemia is excluded. History
             of plasma cell leukemia is not excluded.

          -  Patients who have not received any myeloma therapy for the preceding 6 months, except
             if the last myeloma therapy was a CAR T cell therapy.

          -  At least 14 day washout from myeloma therapies prior to leukapheresis and prior to
             starting lymphodepletion. The washout for experimental treatments would be 5 half
             lives or 14 days (whichever is shorter).

          -  At least 14 day washout from radiation prior to leukapheresis and prior to starting
             lymphodepletion.

          -  Patients treated with previous GPRC5D targeted therapies would be excluded.

          -  Patients with any concurrent active malignancies (or another primary malignancy not in
             remission for at least 2 years) as defined by malignancies requiring any therapy other
             than expectant observation or hormonal therapy, with the exception of squamous and
             basal cell carcinoma of skin.

          -  Patients with a prior allogeneic transplant at least 6 months prior to study
             enrollment ARE eligible UNLESS experienced GvHD that required systemic steroids or
             other systemic lymphotoxic therapy within 12 weeks of initial screening

          -  Patients on systemic steroids (except if solely for adrenal replacement) within two
             weeks of collection

          -  Active auto-immune disease including connective tissue disease, uveitis, sarcoidosis,
             inflammatory bowel disease, or multiple sclerosis, or have a history of severe (as
             judged by the principal investigator) autoimmune disease requiring prolonged
             immunosuppressive therapy

          -  Prior or active CNS involvement by myeloma (e.g. leptomeningeal disease). Screening
             for this, for example, by lumbar puncture, is only required if suspicious symptoms or
             radiographic findings are present.

          -  Pre-existing (active or severe) neurologic disorders (e.g. pre-existing seizure
             disorder)

          -  Active uncontrolled acute infections

          -  Any other issue which, in the opinion of the treating physician, would make the
             patient ineligible for the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximum tolerated dose (MTD)
Time Frame:1 year
Safety Issue:
Description:The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level. All patients treated in a dose cohort will be observed a minimum of 30 days before the T cell dose can be escalated.

Secondary Outcome Measures

Measure:overall response rate (ORR)
Time Frame:approximately 1 and 4 weeks following the T cell infusion
Safety Issue:
Description:Assessed by the IMWG 2016 criteria.The major criteria for determination of response to therapy in patients with MM include examination of the peripheral blood and bone marrow. Bone marrow aspirate and biopsy obtained at approximately 1 and 4 weeks following the T cell infusion will be used for disease response assessment. Definitions for response assessment will be as defined by the pending update to the international myeloma working group (IMWG) guidelines

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Adoptive T cell therapy
  • Chimeric Antigen Receptor
  • 18-367

Last Updated

February 21, 2021