Activated T Lymphocytes Expressing CARs, Relapsed CD19+ Malignancies Post-Allo HSCT(CARPASCIO)

Plain-language summary

This Phase 1 gene transfer study tests CD19.CAR-CD28Z T cells at two dose-escalation levels in patients whose non-Hodgkin lymphoma (NHL), acute lymphocytic leukemia (ALL) or chronic lymphocytic leukemia (CLL) has come back or has not gone away after treatment. The approach combines two ways of fighting disease, the target-binding property of antibodies and the cell-killing ability of T cells. Eligibility requires CD19+ B-ALL or CD19+ B-cell CLL/NHL in the context of allogeneic hematopoietic stem cell transplantation (HSCT), a life expectancy of at least 12 weeks, and an identified appropriate donor.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Active, not recruiting

Sponsor

Baylor College of Medicine

Intervention

CD19.CAR-CD28Z T Cells - dose escalation 2, CD19.CAR-CD28Z T Cells - dose escalation 1

Start date

4/1/2014

Estimated completion

12/1/2030

Countries

United States

Locations

• Houston, United States
• Houston, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

PROCUREMENT

* Group A: CD19+ B-ALL undergoing allogeneic HSCT or Group B: CD19+ B cell CLL or NHL undergoing allogeneic HSCT
* Life expectancy of ≥12 weeks.
* Patient has an appropriate donor identified for hematopoietic stem cell transplantation

TREATMENT

* Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A) OR any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B)
* Residual disease at the time of transplant (bulky or minimal) or post transplant relapse as evidenced by PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood. MRD will be defined as detection in blood or marrow of any of the following:

  * Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient's leukemia cells pre transplant on a post transplant evaluation.
  * An immune globulin rearrangement known to be a disease marker for this patient post transplant.
  * A leukemia specific phenotype post transplant at a level of ≥ 0.01%
  * Mixed donor chimerism (any level)
* Life expectancy ≥ 6 weeks
* Karnofsky/Lansky score ≥ 50%.
* Bilirubin ≤ 2 times the upper limit of normal.
* AST ≤ 3 times the upper limit of normal.
* Estimated GFR \> 50 mL/min
* Hgb ≥ 7.0 (can be a transfused value)
* Pulse oximetry of \> 90% on room air
* Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after ATL infusion. The male partner should use a condom.
* Available allogeneic activated peripheral blood T cell products with \>=15% expression of CD19.CAR-CD28ζ determined by flow cytometry (cell dose is based on total cell numbers and not individual antileukemic cell numbers).
* No other investigational antitumor therapy for one month prior to entry in this study.
* Patients or legal guardians must sign an informed consent.

Exclusion Criteria:

* Severe intercurrent infection.
* Evidence of GVHD \> grade II.
* Pregnant or lactating.
* History of hypersensitivity reactions to murine protein-containing products.
* Currently taking corticosteroids (\>0.5 mg/kg/day prednisone or equivalent) for therapy of GVHD.