- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03070327
BCMA Targeted CAR T Cells With or Without Lenalidomide for the Treatment of Multiple Myeloma
March 1, 2024 updated by: Memorial Sloan Kettering Cancer Center
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)
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCMA Targeted CAR T Cells with or without Lenalidomide
|
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
36 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Sham Mailankody, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 27, 2017
Primary Completion (Estimated)
February 1, 2025
Study Completion (Estimated)
February 1, 2025
Study Registration Dates
First Submitted
February 28, 2017
First Submitted That Met QC Criteria
February 28, 2017
First Posted (Actual)
March 3, 2017
Study Record Updates
Last Update Posted (Estimated)
March 4, 2024
Last Update Submitted That Met QC Criteria
March 1, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Cyclophosphamide
- Lenalidomide
Other Study ID Numbers
- 17-025
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on EGFRt/BCMA-41BBz CAR T cell
-
Xuzhou Medical UniversityRecruiting
-
University College, LondonRecruiting
-
CARsgen Therapeutics Co., Ltd.Active, not recruitingMultiple MyelomaUnited States, Canada
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingMultiple Myeloma | New Diagnosis TumorChina
-
University College, LondonEnrolling by invitationMultiple MyelomaUnited Kingdom
-
Hebei Yanda Ludaopei HospitalGracell Biotechnology Ltd.UnknownMultiple MyelomaChina
-
Hrain Biotechnology Co., Ltd.Shanghai Changzheng HospitalRecruiting
-
Hebei Senlang Biotechnology Inc., Ltd.RecruitingLymphoma | Multiple Myeloma | Acute Lymphoblastic LeukemiaChina
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingRefractory Multiple Myeloma | Relapse Multiple MyelomaChina
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingVasculitis | Amyloidosis | Autoimmune Hemolytic Anemia | POEMS SyndromeChina