BCMA Targeted CAR T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma

NCT03070327 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 17-025
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this phase I clinical trial is to test the safety of these CAR T cells in patients with myeloma. There are two parts of this study. Part 1 of the study consists of screening for BCMA, Lenalidomide assignment and cell collection. Part 2 of the study is treatment with modified CAR T cells.

Conditions

Multiple Myeloma

Keywords

B-cell Maturation Antigen (BCMA); Targeted EGFRt/BCMA-41BBz; Chimeric antigen receptor (CAR); Lenalidomide; 17-025

Outcome Measures

Primary Outcomes (1)

• MTD of gene-modified T cells

  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. T cell dose may be divided in up to three infusions administered over up to 7 days.

  36 months

Study Arms (1)

BCMA Targeted CAR T Cells with or without Lenalidomide

EXPERIMENTAL

Biological: EGFRt/BCMA-41BBz CAR T cell; Drug: Cyclophosphamide; Drug: Lenalidomide.

Interventions

Lenalidomide. DRUG

A cohort of patients will be treated with CAR T cell therapy and concomitant Lenalidomide. 10mg PO 21/28 days will be started no less then 1 week prior to clinical apheresis.

BCMA Targeted CAR T Cells with or without Lenalidomide

EGFRt/BCMA-41BBz CAR T cell BIOLOGICAL

Modified T cell infusions will be administered 2-7 days following the completion of conditioning chemotherapy.There are 3 planned dose levels for this study: 1x10\^6, 3x10\^6, and 1x10\^7 EGFRt/BCMA-41BBz CAR T cells/kg, and a dose -1 level at 3x10\^5 EGFRt/BCMA-41BBz CAR T cells/kg, if needed; each dose cohort will consist of 3-6 patients.

BCMA Targeted CAR T Cells with or without Lenalidomide

Cyclophosphamide DRUG

Cyclophosphamide 3000 mg/m2 IV once on day -7 to -2 or low intensity cy/flu (cyclophosphamide 300 mg/m2/day x 3 + fludarabine 30 mg/m2/day x 3) with the last day occurring on day -7 to -2 are the default options for is the default conditioning chemotherapy.

BCMA Targeted CAR T Cells with or without Lenalidomide

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, with MM cells expressing BCMA, previously treated with 2+ prior lines of therapy including an IMiD and a PI, either with refractory, persistent, or progressive disease
• Age ≥ 18 years of age
• Creatinine ≤2.0 mg/dL, direct bilirubin ≤2.0 mg/dL, AST and ALT ≤3.0x upper limit of normal (ULN)
• Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.
• HGB≥7g/dl, ANC≥1,000/mm3, Platelet≥30,000/mm3 without transfusion or growth factor support for at least 1 week
• M spike ≥0.5 g/dL or involved free light chain ≥10 mg/dL with an abnormal free light chain ratio

You may not qualify if:

• Karnofsky performance status \<70
• Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished
• Impaired cardiac function (LVEF \<40%) as assessed by ECHO or MUGA scan
• 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
• Patients with any concurrent active malignancies 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 ARE eligible UNLESS previously or currently experienced GvHD that required systemic steroids or other systemic lymphotoxic therapy
• 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 treatment with gene modified T cells
• Prior or active CNS involvement by myeloma (eg leptomeningial disease). Screening for this, for example, by lumbar puncture, is only required if suspicious symptoms or radiographic findings are present

Sponsors & Collaborators

• Juno Therapeutics, Inc., a Bristol-Myers Squibb Company: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Jain T, Knezevic A, Pennisi M, Chen Y, Ruiz JD, Purdon TJ, Devlin SM, Smith M, Shah GL, Halton E, Diamonte C, Scordo M, Sauter CS, Mead E, Santomasso BD, Palomba ML, Batlevi CW, Maloy MA, Giralt S, Smith E, Brentjens R, Park JH, Perales MA, Mailankody S. Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies. Blood Adv. 2020 Aug 11;4(15):3776-3787. doi: 10.1182/bloodadvances.2020002509.

  PMID: 32780846 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; Lenalidomide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sham Mailankody, MD

  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 is an open-label, dose escalating, nonrandomized, single-center, phase I study of EGFRt/BCMA-41BBz CAR T cells in patients with a diagnosis of MM. Dose escalation will follow a standard 3-by-3 escalation design. Cohorts of 3-6 patients will be infused with escalating doses of EGFRt/BCMA-41BBz CAR T cells to establish the maximum tolerated dose (MTD). After a dose level has been determined safe to escalate (DLT in 0/3 or 1/6 patients), a parallel cohort at that dose level will be conducted while patients are taking Lenalidomide.

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 3, 2017
• Study Start: February 27, 2017
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)