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

NCT04555551 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 18-367
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose (MTD)

  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.

  1 year

Secondary Outcomes (1)

• overall response rate (ORR)

  approximately 1 and 4 weeks following the T cell infusion

Study Arms (1)

Targeted MCARH109 CAR Modified T cells

EXPERIMENTAL

Patients 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.

Biological: Infusion of MCARH109 T cells

Interventions

Infusion of MCARH109 T cells BIOLOGICAL

Patients will be admitted to Memorial Hospital as inpatient prior to the infusion of CAR T cells. The T cell infusion will be planned to start at 2 days following the completion of the conditioning chemotherapy (up to 7 days is allowed if clinically indicated to delay).Cohorts of 3-6 patients each will be treated with escalating doses of modified T cells.

Targeted MCARH109 CAR Modified T cells

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited protocol activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited protocol activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited protocol activities)

Uniondale, New York, 11553, United States

Location

Related Publications (2)

• Jurgens EM, Firestone RS, Chaudhari J, Hosszu K, Devlin SM, Shah UA, Landa J, McAvoy DP, Lesokhin AM, Korde N, Hassoun H, Tan CR, Hultcrantz M, Shah GL, Landau HJ, Chung DJ, Scordo M, Eren OC, Dogan A, Giralt SA, Park JH, Riviere I, Brentjens RJ, Smith EL, Wang X, Usmani SZ, Mailankody S. Phase I Trial of MCARH109, a G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D)-Targeted Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: An Updated Analysis. J Clin Oncol. 2025 Feb 10;43(5):498-504. doi: 10.1200/JCO-24-01785. Epub 2024 Dec 4.

  PMID: 39631041 DERIVED

• Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald L, Cadzin B, Wang X, Sikder D, Senechal B, Bermudez VP, Purdon TJ, Hosszu K, McAvoy DP, Farzana T, Mead E, Wilcox JA, Santomasso BD, Shah GL, Shah UA, Korde N, Lesokhin A, Tan CR, Hultcrantz M, Hassoun H, Roshal M, Sen F, Dogan A, Landgren O, Giralt SA, Park JH, Usmani SZ, Riviere I, Brentjens RJ, Smith EL. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022 Sep 29;387(13):1196-1206. doi: 10.1056/NEJMoa2209900.

  PMID: 36170501 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

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

Study Officials

• Sham Mailankody, MBBS

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This phase I trial will follow a standard 3-by-3 dose escalation design.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 18, 2020
• Study Start: September 8, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (7)