Administration of Donor Multi TAA-Specific T Cells for AML or MDS (ADSPAM)

NCT02494167 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: H-36346 ADSPAM
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

This research study uses special blood cells called multiple tumor-associated antigen (TAA)-specific T cells (a new experimental therapy) to treat patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) 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 causes 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 cancer cell, so they either do not show up, or show up in low quantities, or 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, NY-ESO-1, PRAME, and Survivin, which are expressed on most AML and MDS cancer cells. The cells will be infused at least 30 days post-allogeneic stem cell transplant. In this study, the investigators want see whether these cells will be able to recognize and kill cancer cells that express these proteins. 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 tumor protein multiTAA-specific T cells for patients with AML or MDS.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndrome; MultiTAA Specific T cells

Outcome Measures

Primary Outcomes (1)

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

  Maximum tolerated dose (MTD) of multiTAA-specific T cells among the five 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 AML or MDS

Biological: MultiTAA-specific T cells

Group B

EXPERIMENTAL

Treatment with donor-derived multiTAA-specific T cells for relapsed/residual disease following HSCT for AML or MDS

Biological: MultiTAA-specific T cells

Interventions

MultiTAA-specific T cells BIOLOGICAL

The 5 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; Dose Level Four: 5 x 10e7 cells/m2; Dose Level Five: 1 x 10e8 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 central lie. In patients being treated as adjuvant therapy or if patients with residual disease, have a complete response or stable disease, they will be eligible to receive up to 6 further doses of multiTAA-specific T cells at the same dose as the initial infusions (or below the patient's original dose can be administered) at least 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:

• Patients will be eligible to receive donor-derived multiTAA-specific T cells following any type of allogeneic HSCT as;
• (i) Adjuvant therapy for AML/MDS (Group A) or
• (ii) Treatment for refractory/relapsed or minimal residual AML/MDS 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, in the peripheral blood or any other extramedullary sites.
• Minimal residual disease (MRD) will be defined as detection in blood, bone marrow, or other tissues of any of the following:
• (i) Any leukemia specific marker such as t(8;21); inv 16; t (15;17), t(9;22) or t(4;11) documented in the patient's leukemia cells pre-transplant on a post-transplant evaluation.
• (ii) Expression of a leukemia associated antigen known to be a marker for residual disease like WT1.
• (iii) A leukemia-specific phenotype (e.g. expression of markers including CD13 and/or CD33 and/or CD117 and/or HLA-DR+) post-transplant at a level of ≥ 0.01%.
• (ix) Mixed donor chimerism (\> 20%).
• Life expectancy ≥ 6 weeks.
• Karnofsky/Lansky score of ≥ 50.
• Patient or parent/guardian capable of providing informed consent.
• Bilirubin ≤ 2X upper limit of normal.
• AST ≤ 3X upper limit of normal.
• Undergoing stem cell transplant at CAGT.

You may not qualify if:

• Patients receiving ATG or Campath within 28 days of infusion.
• Patients receiving a Donor Lymphocyte Infusion within 4 weeks of planned T cell infusion.
• Less than 30 days post-allogeneic stem cell transplant.
• Severe intercurrent infection.
• Evidence of GVHD \> Grade II.
• Pregnant or lactating.
• Currently taking corticosteroids (\> 0.5 mg/kg/day prednisone or equivalent).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• American Society for Blood and Marrow Transplantation (ASBMT): collaborator
• Cancer Prevention Research Institute of Texas: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Lulla PD, Naik S, Vasileiou S, Tzannou I, Watanabe A, Kuvalekar M, Lulla S, Carrum G, Ramos CA, Kamble R, Hill L, Randhawa J, Gottschalk S, Krance R, Wang T, Wu M, Robertson C, Gee AP, Chung B, Grilley B, Brenner MK, Heslop HE, Vera JF, Leen AM. Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant. Blood. 2021 May 13;137(19):2585-2597. doi: 10.1182/blood.2020009471.

  PMID: 33270816 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Premal Lulla, 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: July 8, 2015
• First Posted: July 10, 2015
• Study Start: February 1, 2016
• Primary Completion: April 1, 2025
• Study Completion (Estimated): February 1, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)