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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase

Active, not recruiting

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: Lenalidomide.

Biological: EGFRt/BCMA-41BBz CAR T cell

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03070327

17-025

Details and patient eligibility

About

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.

Enrollment

20 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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
Plasma cell leukemia
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
Patients who previously had any intolerance to Lenalidomide 10 mg or who have a contraindication to Lenalidomide will not be eligibile for concominant treatment with Lenalidomide but will remain eligible for CAR T cell therapy without Lenalidomide.