NCT02475707: STELLA

Administration of Donor-Derived Multi-Tumor-Associated Antigen (TAA)-Specific T Cells to Patients With ALL

Completed Phase 1 Last updated 4 December 2024

What this trial tests

Phase 1 trial testing MultiTAA-specific T cells in Leukemia, Lymphoblastic (Acute) in 40 participants. Completed in 18 November 2024.

Timeline

1 February 2016

Primary endpoint
29 October 2019

18 November 2024

Quick facts

Lead sponsor	Baylor College of Medicine
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	40
Start date	1 February 2016
Primary completion	29 October 2019
Estimated completion	18 November 2024
Sites	2 locations across United States

Drugs / interventions tested

• MultiTAA-specific T cells — full drug profile →

Conditions studied

• Leukemia, Lymphoblastic (Acute) — all drugs for Leukemia, Lymphoblastic (Acute) →

Sponsor

Baylor College of Medicine

Who can join

Eligibility, any sex, with Leukemia, Lymphoblastic (Acute). Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of patients with dose-limiting toxicities (DLTs).
  Time frame: 4 weeks
  Maximum tolerated dose (MTD) of multiTAA-specific T cells among the three pre-specified dose levels.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?
   Al-Khadairi G, Decock J. · · 2019 · cited 85× · PMID 31311081 · DOI 10.3390/cancers11070984
2. The twisted survivin connection to angiogenesis.
   Sanhueza C, Wehinger S, Castillo Bennett J, Valenzuela M, et al · · 2015 · cited 56× · PMID 26584646 · DOI 10.1186/s12943-015-0467-1
3. Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer.
   Nin DS, Deng LW. · · 2023 · cited 45× · PMID 36980267 · DOI 10.3390/cells12060926
4. T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies.
   Janelle V, Rulleau C, Del Testa S, Carli C, et al · · 2020 · cited 36× · PMID 32153583 · DOI 10.3389/fimmu.2020.00276
5. T cell optimization for graft-versus-leukemia responses.
   Biernacki MA, Sheth VS, Bleakley M. · · 2020 · cited 31× · PMID 32376800 · DOI 10.1172/jci.insight.134939
6. Donor-derived multiple leukemia antigen-specific T-cell therapy to prevent relapse after transplant in patients with ALL.
   Naik S, Vasileiou S, Tzannou I, Kuvalekar M, et al · · 2022 · cited 22× · PMID 35134127 · DOI 10.1182/blood.2021014648
7. Antigen Targets for the Development of Immunotherapies in Leukemia.
   Bauer J, Nelde A, Bilich T, Walz JS. · · 2019 · cited 12× · PMID 30897713 · DOI 10.3390/ijms20061397
8. The application, safety, and future of <i>ex vivo</i> immune cell therapies and prognosis in different malignancies.
   Einloth KR, Gayfield S, McMaster T, Didier A, et al · · 2023 · cited 2× · PMID 38022382 · DOI 10.34172/bi.2023.27521