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CART-19 Post-ASCT for Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02794246
Recruitment Status : Terminated (Study was terminated due to administrative reasons.)
First Posted : June 9, 2016
Last Update Posted : July 3, 2019
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE June 6, 2016
First Posted Date  ICMJE June 9, 2016
Last Update Posted Date July 3, 2019
Actual Study Start Date  ICMJE June 2016
Actual Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2016)
Evaluate Progression Free Survival [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02794246 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE CART-19 Post-ASCT for Multiple Myeloma
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Biological: CART-19 cells
Study Arms  ICMJE Experimental: Single Arm
Intervention: Biological: CART-19 cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 1, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: June 6, 2016)
Actual Study Completion Date  ICMJE May 2019
Actual Primary Completion Date February 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

    1. 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).
    2. 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:

    1. Left ventricular ejection fraction ≥ 40%,
    2. AST/ALT ≤2.5 times the upper limit of normal
    3. Total bilirubin ≤1.5 mg/dL, unless hyperbilirubinemia is attributable solely to Gilbert's syndrome.
    4. Estimated (by CKD-EPI or Cockgroft-Gault equations) or calculated CrCl ≥40 ml/min.
    5. 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.

    1. Serum M-spike ≥ 0.5 g/dL
    2. 24 hr urine M-spike ≥ 200mg
    3. Involved serum FLC ≥ 50 mg/L with abnormal ratio
    4. 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02794246
Other Study ID Numbers  ICMJE UPCC 19416, 824655
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Alfred Garfall, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP