- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02794246
CART-19 Post-ASCT for Multiple Myeloma
Phase 2 Study Of Autologous T Cells Engineered To Express an Anti-CD19 Chimeric Antigen Receptor (CART-19) Following First-line Autologous Stem Cell Transplantation for High-risk Multiple Myeloma
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subjects must be age 18-70, inclusive, at time of enrollment.
- Subjects must have ECOG performance status of 0-2.
Subjects must have a confirmed diagnosis of active multiple myeloma according to IMWG criteria, summarized below in Table 6. For circumstances not encompassed by this summary of the diagnostic criteria, reference can be made to the full publication of the IMWG criteria67. In addition, subjects must have "high-risk" multiple myeloma according to one of the following criteria:
- Any of the following high-risk cytogenetic features, documented by FISH or metaphase karyotyping: deletion 17p, t(4;14), t(14;16), t(14;20).
- Standard-risk cytogenetics but elevated LDH and beta-2-microglobulin > 5.5 mg/L (i.e., R-ISS stage III).
- At time of enrollment, subjects must be within 9 months of initiation of systemic therapy for multiple myeloma.
- Requirements for pre-enrollment therapy: Subjects must have received or be receiving, at time of enrollment, "RVD" therapy (combination therapy with lenalidomide, bortezomib, and dexamethasone). Patients must have received ≤6 cycles of RVD at time of enrollment and must not have progressed (by IMWG criteria65) on RVD. Patients may have received other regimens prior to RVD if such therapy was limited to ≤3 cycles. Patients may have received radiation therapy prior to enrollment. Patients must not have received infusional chemotherapy (e.g., VTD-PACE or similar regimen) prior to enrollment.
Subjects must be eligible for ASCT and to receive a melphalan dose of 200 mg/m2 as defined by the following criteria:
- Left ventricular ejection fraction ≥ 40%,
- AST/ALT ≤2.5 times the upper limit of normal
- Total bilirubin ≤1.5 mg/dL, unless hyperbilirubinemia is attributable solely to Gilbert's syndrome.
- Estimated (by CKD-EPI or Cockgroft-Gault equations) or calculated CrCl ≥40 ml/min.
- DLCO ≥50% of predicted after correction for anemia.
Subjects must have measurable disease by standard serum and urine tests to enable post-transplant monitoring for progression-free survival. Any of the following criteria are sufficient to define measurable disease.
- Serum M-spike ≥ 0.5 g/dL
- 24 hr urine M-spike ≥ 200mg
- Involved serum FLC ≥ 50 mg/L with abnormal ratio
- For IgA multiple myeloma, total serum IgA level elevated above normal range. Note: Measurable disease does not need to be documented at enrollment but can be based on historical lab results obtained at or since diagnosis with multiple myeloma. For example, a patient who does not have measurable disease at enrollment due to complete remission after induction therapy is eligible if the disease was previously measurable by one of the above criteria.
- Subjects must have signed written, informed consent.
- Subjects of reproductive potential must agree to use acceptable birth control methods
Exclusion Criteria:
- Subjects must not:
Be pregnant or lactating. Have inadequate venous access for or contraindications to leukapheresis. Have any active and uncontrolled infection. Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined.
Have NYHA Class III or IV heart failure (see Appendix 2), unstable angina, or a history of recent (within 6 months) myocardial infarction or sustained (>30 seconds) ventricular tachyarrhythmias.
Have undergone allogeneic stem cell transplantation. Have received prior gene therapy or gene-modified cellular immunotherapy. Have 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.
Have prior or active central nervous system (CNS) involvement (e.g. leptomeningeal disease, parenchymal masses) with myeloma. Screening for this (e.g. with lumbar puncture) is not required unless suspicious symptoms are present.
Have a contraindication to post-ASCT maintenance lenalidomide. Have active infection with HIV (negative HIV 1/2 antibody screen), hepatitis C (negative hepatitis C antibody screen), or hepatitis B (negative hepatitis B surface antigen). Any positive serologies for HIV or viral hepatitis should be confirmed with appropriate confirmatory testing before concluding that an active infection is present. Subjects with positive hepatitis core antibody are also excluded since the effect of long-term B cell depletion on the risk of hepatitis B reactivation is unknown.
Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
Study Plan
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 |
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Experimental: Single Arm
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Evaluate Progression Free Survival
Time Frame: Follow progression-free survival (PFS) for 2-3 years post CART-19 infusion
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Progression free survival as defined by Partial Response (PR); Stable Disease (SD); Very Good Partial Response (VGPR), and Stringent Complete Response (sCR) to treatment.
The outcome measures range from Stable disease to Stringent Complete Response (SD worst outcome; sCR best outcome
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Follow progression-free survival (PFS) for 2-3 years post CART-19 infusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alfred Garfall, MD, Abramson Cancer Center at Penn Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
Other Study ID Numbers
- UPCC 19416, 824655
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
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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
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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
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Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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