Clinical trial NCT03070327: BCMA Targeted CAR T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma
Official title: A Phase I Trial of B-cell Maturation Antigen (BCMA) Targeted EGFRt/BCMA-41BBz Chimeric Antigen Receptor (CAR) Modified T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: B-cell Maturation Antigen (BCMA)
Targeted EGFRt/BCMA-41BBz
Chimeric antigen receptor (CAR)
Lenalidomide
17-025
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
First posted: 2017-03-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: MTD of gene-modified T cells
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sham Mailankody, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.