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

This study is currently recruiting participants.
See Contacts and Locations
Verified September 2017 by Memorial Sloan Kettering Cancer Center
Sponsor:
Collaborator:
Juno Therapeutics, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT03070327
First received: February 28, 2017
Last updated: September 7, 2017
Last verified: September 2017
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma Biological: EGFRt/BCMA-41BBz CAR T cell Drug: Cyclophosphamide Drug: Lenalidomide. Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • MTD of gene-modified T cells [ Time Frame: 36 months ]
    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.


Estimated Enrollment: 36
Actual Study Start Date: February 27, 2017
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BCMA Targeted CAR T Cells with or without Lenalidomide Biological: EGFRt/BCMA-41BBz CAR T cell
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.
Drug: Cyclophosphamide
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.
Drug: Lenalidomide.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03070327

Contacts
Contact: Claudia Diamonte (212) 639-5317 DiamontC@mskcc.org
Contact: Craig Sauter, MD 212-639-3460

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sham Mailankody, MD    212-639-2131      
Contact: Craig Sauter, MD    212-639-3460      
Principal Investigator: Sham Mailankody, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Juno Therapeutics, Inc.
Investigators
Principal Investigator: Sham Mailankody, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03070327     History of Changes
Other Study ID Numbers: 17-025
Study First Received: February 28, 2017
Last Updated: September 7, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
B-cell Maturation Antigen (BCMA)
Targeted EGFRt/BCMA-41BBz
Chimeric antigen receptor (CAR)
Lenalidomide
17-025

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Lenalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017