Administration of Donor MultiTAA-Specific T Cells for ALL

NCT02475707 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: H-37042 STELLASTELLA
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This study uses special blood cells called multiple tumor-associated antigen (TAA)-specific T cells to treat patients with acute lymphoblastic leukemia (ALL) which has come back, or may come back, or has not gone away after standard treatment, including an allogeneic hematopoietic stem cell transplant (HSCT). The investigators have previously used this sort of therapy to treat Hodgkin or non-Hodgkin lymphomas that are infected with Epstein-Barr virus (EBV). EBV is found in cancer cells of up to half of all patients with Hodgkin and non-Hodgkin lymphoma. This suggests that it may play a role in causing lymphoma. The cancer cells infected by EBV are able to hide from the body's immune system and escape being killed. The investigators previously tested whether special white blood cells (called T cells) that were trained to kill EBV-infected cells could affect these tumors, and in many patients the investigators found that giving these trained T cells caused a complete or partial response. Other cancers express specific proteins that can be targeted in the same way. The investigators have been able to infuse such tumor-targeted cells into up to 10 patients with lymphoma who do not have EBV, and seen some complete responses. Importantly, the treatment appears to be safe. Therefore, the investigators now want to test whether the investigators can direct these special T cells against other types of cancers that carry similar proteins called tumor-associated antigens (TAAs). These proteins are specific to the leukemia cell, so they either do not show up, or show up in low quantities, on normal human cells. The investigators will grow T cells from patients' stem cell donors in the laboratory in a way that will train them to recognize the tumor proteins WT1, PRAME and Survivin, which are expressed on most ALL cancer cells. The cells will be infused at least 30 days post-allogeneic HSCT. In this study, the investigators want to see whether these cells will be able to recognize and kill leukemia cells that express these antigens. These donor-derived multiTAA-specific T cells are an investigational product not yet approved by the U.S. Food and Drug Administration. The purpose of this study is to find the largest safe dose of donor-derived multiTAA-specific T cells for patients with ALL.

Conditions

Leukemia, Lymphoblastic (Acute)

Keywords

leukemia; lymphoblastic; ALL; multiTAA-specific T cells; HSCT

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose-limiting toxicities (DLTs).

  Maximum tolerated dose (MTD) of multiTAA-specific T cells among the three pre-specified dose levels.

  4 weeks

Secondary Outcomes (2)

• Number of patients with a decrease in the marker of disease.

  4 weeks

• Median number of T cells post-infusion.

  1 year

Study Arms (2)

Group A

EXPERIMENTAL

Treatment with donor-derived multiTAA-specific T cells as adjuvant therapy following HSCT for ALL.

Biological: MultiTAA-specific T cells

Group B

EXPERIMENTAL

Treatment with donor-derived multiTAA-specific T cells for relapsed/residual disease following HSCT for ALL.

Biological: MultiTAA-specific T cells

Interventions

MultiTAA-specific T cells BIOLOGICAL

The 3 dose levels are: Dose Level 1: 5 x 10e6 cells/m2; Dose Level 2: 1 x 10e7 cells/m2; Dose Level 3: 2 x 10e7 cells/m2 The T cells are given from 30 days post-HSCT. They are administered by intravenous injection over 1-10 minutes through either a peripheral or a central line. Patients being treated on Arm A (adjuvant) or Arm B (active disease) who have a partial response, complete response or stable disease, will be eligible to receive up to 6 further doses of multiTAA-specific T cells at the same dose as the initial infusions at a minimum of 4 weeks apart.

Also known as: Multiple tumor-associated antigen (TAA)-specific T cells

Group A; Group B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Only patients who receive infusions in the integrated Cell and Gene Therapy (CAGT) Transplant program at Texas Children's Hospital (TCH) or Houston Methodist Hospital (HMH) are eligible for this study.
• Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as:
• (i) Adjuvant therapy for ALL (Group A), or (ii) Treatment for relapsed/residual ALL disease (Group B)
• Residual disease at the time of transplant or post-transplant relapse is defined as PCR positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry, or increased blasts on bone marrow biopsy or in the peripheral blood. Minimal residual disease (MRD )will be defined as detection in blood or marrow of any of the following:
• (i) Any leukemia-specific marker (such as t(12;21); t(9;22) or t(4;11)) documented in the patient's leukemia cells pre-transplant on a post-transplant evaluation.
• (ii) A leukemia-specific phenotype (e.g. expression of markers including CD10 and/or CD19 or CD3 and/or CD4 or CD8) post-transplant at a level greater than or equal to 0.01%.
• (iii) Mixed donor chimerism (greater than 20%).
• Life expectancy greater than or equal to 6 weeks.
• Karnofsky/Lansky score of greater than or equal to 50.
• Patient or parent/guardian capable of providing informed consent.
• Bilirubin less than or equal to 2X upper limit of normal.
• AST less than or equal to 3X upper limit of normal.
• Serum creatinine less than or equal to 2X upper limit of normal.
• Hgb greater than or equal to 7.0 g/dL (can be transfused).
• Pulse oximetry of greater than 90% on room air.

You may not qualify if:

• Patients receiving ATG or Campath within 28 days of infusion.
• Patients receiving a Donor Lymphocyte Infusion (DLI) within 4 weeks of planned T cell infusion.
• Less than 30 days post-allogeneic stem cell transplant.
• Severe intercurrent infection.
• Evidence of GVHD greater than Grade II.
• Pregnant or lactating.
• Currently taking corticosteroids (greater than 0.5 mg/kg/day prednisone or equivalent).
• Donor Eligibility:
• Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants who have fulfilled eligibility for and consented to stem cell donation as per the stem cell transplant program's standard operating procedures. Subjects must be at least 12 kg or 24 pounds to be eligible for stem cell donation. The stem cell donor will have already been selected by the primary Bone Marrow Transplant attending according to CAGT SOPs for Donor Evaluation, Donor Selection, and Donor Deferral. If a donor has been chosen for the transplant based on urgent medical need, that same donor will also be used for T cell generation, provided that there are no new reasons for ineligibility since the stem cell collection. In this study, the subject's hematopoietic stem cell donor will also be the donor for the T cells.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bilal Omer, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 12, 2015
• First Posted: June 19, 2015
• Study Start: February 1, 2016
• Primary Completion: October 29, 2019
• Study Completion: November 18, 2024
• Last Updated: December 6, 2024

Record last verified: 2024-12

Locations

US (2)