MEMCAR19: Allogeneic CAR T-Cell Therapy for Relapsed/Refractory CD19-Positive Leukemia

MEMCAR19 is a phase 1 clinical trial evaluating the safety and maximum tolerated dose (MTD) of a novel CAR T-cell product, allogeneic CD19-CAR.CD45RA-negative T cells, for the treatment of children and young adults with relapsed and/or refractory CD19-positive leukemia. The CAR T-cell product will be manufactured at the St. Jude Children’s Research Hospital Good Manufacturing Practices facility.

In this study, the CD45RA-positive T cells will be depleted prior to CD19-CAR T-cell production and the resultant memory T cells will be used to manufacture a CD19-CAR T cell product. The goals of this approach are to increase the availability of CAR T-cell therapy for patients through the use of an allogeneic platform, while using T-cell selection techniques to decrease the risk of graft-versus-host-disease (GVHD).

Patients will be enrolled in 1 of 2 cohorts:

• Cohort A – Patient has relapsed and/or refractory CD19-positive leukemia, and patient has previously received a hematopoietic cell transplant from the selected CAR-T donor.
• Cohort B – Patient has relapsed and/or refractory CD19-positive leukemia and is not suitable to receive autologous CD19-CAR T-cell therapy because they:
  • Have relapsed and/or refractory disease despite prior treatment with autologous CD19-CAR T-cell therapy
  • Have a history of prior autologous leukapheresis failure
  • Have a history of prior autologous CAR T-cell manufacturing failure
  • Are unable to undergo autologous leukapheresis in the opinion of the study PI(s). Examples may include: patient has a small size or low weight, inadequate T-cell counts, rapidly progressive leukemia, or a clinical status not amenable to apheresis.

Treatment will include a single treatment course, including a lymphodepleting chemotherapy regimen (fludarabine/cyclophosphamide), followed by a single infusion of allogeneic CD19-CAR.CD45RA-negative T cells. Once the MTD is determined for a given cohort, enrollment on an expansion group will begin. Total study duration for each patient will be 1 year. Following the study period, patients will enroll on the St. Jude  long-term follow-up protocol.

Primary Objective

• To determine the maximum tolerated dose and characterize the safety profile and dose-limiting toxicities of treatment with allogeneic CD19-CAR.CD45RA-negative T cells in pediatric patients with relapsed and/or refractory CD19-positive leukemia

Secondary Objectives Include:

• To evaluate the anti-leukemic activity of allogeneic CD19-CAR.CD45RA-negative T cells
• To determine rates and severity of GVHD after treatment with allogeneic CD19-CAR.CD45RA-negative T cells

Eligibility Criteria

Inclusion criteria include:

Donor eligibility

• At least 18 years old
• At least single haplotype matched family member
• HIV negative
• Not pregnant or breastfeeding

Recipient eligibility

• 21 years old or younger
• Diagnosed with relapsed and/or refractory CD19-positive leukemia
• Cohort A only – Patient has relapsed and/or refractory CD19-positive leukemia, and patient has previously received a hematopoietic cell transplant from the selected CAR-T donor
• Cohort B only: Not suitable to receive autologous CD19-CAR T-cell therapy (as defined in the study)
• Detectable medullary leukemia

Exclusion Criteria include:

• Pregnant or breastfeeding
• History of HIV infection

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

About this study

This research study tests a new treatment for children and young adults with CD19-positive leukemia that has been difficult to treat or has come back after other therapies.

The treatment in this study is called CAR T-cell therapy. It is a type of immunotherapy. Scientists insert a CAR (chimeric antigen receptor) into T cells to allow them to better find and kill the cancer. The CAR T-cell therapy in this study uses memory T cells collected from a donor. The donor will be a parent or other close family member. Researchers will collect T cells from the donor and use them to manufacture a new product called memory CAR T cells. The use of memory CAR T cells is experimental, which means it is not approved by the U.S. Food and Drug Administration. However, similar CARs have been tested using patient T cells.

If you take part in this study, you will receive an infusion of CAR T cells that were made using memory T cells collected from your donor. Chemotherapy is often given for several days before the infusion. You will stay in the hospital for about a week.

You may or may not benefit from being in this study. But information gained from the study may help future patients with this type of leukemia.

Purpose of this clinical trial

The main goal of this study is to learn the largest dose of memory CAR T cells that can be safely given. Researchers also want to learn about the way memory CAR T cells act in the body and how effectively they treat this type of cancer.

Eligibility overview

Donor eligibility includes:

• At least 18 years old
• At least single haplotype matched family member

Recipient eligibility includes:

•  21 years old or younger
• Diagnosed with relapsed and/or refractory CD19-positive leukemia
• Cohort A only – Patient has relapsed and/or refractory CD19-positive leukemia and patient has previously received a hematopoietic cell transplant from the selected CAR-T donor
• Cohort B only: Not suitable for autologous CD19-CAR T-cell therapy (as defined in the study)
  
• Detectable medullary leukemia