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

University of Pennsylvania1 site in 1 country6 target enrollmentJune 2016

ConditionsMultiple Myeloma

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Multiple Myeloma
Sponsor: University of Pennsylvania
Enrollment: 6
Locations: 1
Primary Endpoint: Evaluate Progression Free Survival
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This will be a single-arm, open-label study. Patients will be enrolled during induction therapy for multiple myeloma, prior to standard-of-care consolidation with autologous stem cell transplantation (ASCT). T cells will be harvested for T cell manufacturing prior to ASCT, and CART-19 will be infused at day ~60 post-ASCT, 3 days after lymphodepleting chemotherapy. The primary endpoint is progression-free survival (PFS) after ASCT. As detailed below, the study is powered to detect an increase in two-year PFS to ~75% from a baseline expectation of 55% based on historical data. Secondary endpoints will evaluate CART-19 persistence and function, minimal residual disease, immune correlative endpoints, and associations of progression-free survival (PFS) with CART-19 persistence and clinical and biologic characteristics of multiple myeloma.

Registry

clinicaltrials.gov

Start Date

June 2016

End Date

May 2019

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Pennsylvania

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must be age 18-70, inclusive, at time of enrollment.
•Subjects must have ECOG performance status of 0-
•Subjects must have a confirmed diagnosis of active multiple myeloma according to IMWG criteria, summarized below in Table
•For circumstances not encompassed by this summary of the diagnostic criteria, reference can be made to the full publication of the IMWG criteria
•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:

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.

Outcomes

Primary Outcomes

Evaluate Progression Free Survival

Time Frame: Follow progression-free survival (PFS) for 2-3 years post CART-19 infusion

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