A Study of TSC-100 and TSC-101 in AML, ALL and MDS Patients Undergoing Haploidentical Donor Transplantation

  • STATUS
    Recruiting
  • End date
    Jun 19, 2025
  • participants needed
    63
  • sponsor
    TScan Therapeutics, Inc.
Updated on 4 October 2022
Accepts healthy volunteers

Summary

This is a multi-center, non-randomized, concurrent controlled, multi-arm, Phase 1 interventional, open-label, biologic assignment-based umbrella study evaluating the feasibility, safety and preliminary efficacy of an escalating dose regimen of up to 2 doses of TSC-100 and TSC-101 in patients with AML, MDS, or ALL following HCT from a haploidentical donor.

Description

A multi-center, non-randomized, controlled, multi-arm, Phase 1 interventional, open label, biologic assignment-based umbrella study is planned to evaluate the feasibility, safety, and preliminary efficacy of repeated dose regimen of up to 2 doses of TSC-100 and TSC-101 (TSC-100 and TSC-101 is a genetically engineered, donor-derived T cell targeting HA-1 and HA-2 respectively) in patients with AML, MDS, or ALL following HCT from a haploidentical donor. The primary objective of this study is to investigate the safety of single and repeated dosing of TSC-100 and TSC-101 in HLA A*02:01 positive patients undergoing haploidentical allogeneic peripheral blood hematopoietic cell transplantation and determine the optimally tolerated dose range. The primary endpoints are: (1) incidence of dose-limiting toxicities (DLTs), and (2) incidence of adverse events (AEs) and serious AEs (SAEs) of TSC-100 and TSC-101 combined with the standard of care (SOC) compared with the SOC alone at 2 years of follow-up. The study will also investigate the efficacy of TSC-100 and TSC-101 combined with the SOC compared with that of the SOC alone to treat the study population and assess the immunogenicity of TSC-100 and TSC-101.

Depending on the HLA type and minor antigen positivity, patients will receive either TSC-100 or TSC-101 combined with the SOC or only SOC. TSC-100 or TSC-101 will be administered intravenously. Standard of care will include reduced intensity conditioning (RIC), hematopoietic cell infusion, and acute graft-versus-host disease (GvHD) prophylaxis. Patients will undergo one of the following RIC regimens, following standard institutional procedures: fludarabine+cyclophosphamide+total body irradiation, fludarabine+melphalan+/-total body irradiation, or thiotepa+busulfan+fludarabine. In addition, patients may receive other supportive care measures and infectioous prophylaxis as necessary, according to institutional guidelines or standards.

Successive cohorts of patients in the treatment arms will be started according to an interval 3+3 (i3+3) dose escalation design. Once the RP2D is identified, up to 15 additional patients may be enrolled in an expansion cohort at the RP2D. Dose escalations to the next cohort of TSC-100 and TSC-101 will be considered after the safety review committee (SRC) establishes reasonable safety for all patients enrolled into the current cohort. The safety and necessity of repeat dosing will also be determined by the SRC.

The safety data for all patients that received at least one dose of TSC-100 or TSC-101 in the treatment arms will be included in the safety assessment to proceed to the next dosing level and the dose escalation meeting will occur when the last patient in the cohort completes the 40-day DLT evaluation period. Depending on the number of DLTs observed, the range of patients that could be enrolled in the dose escalation stage of this i3+3 study is 27 to 108, including patients in the control arm.

Details
Condition AML, Myelodysplastic Syndromes, ALL, Adult
Treatment Control, SOC + TSC-100, SOC + TSC-101
Clinical Study IdentifierNCT05473910
SponsorTScan Therapeutics, Inc.
Last Modified on4 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Participants with evidence of clinically significant infection or uncontrolled viral r reactivation of cytomegalovirus (CMV), Epstein-Barr virus (EBV), Adenovirus, BK virus (BKV), or human herpesvirus 6 (HHV-6)
Participants with active cardiac disease, defined as
Uncontrolled or symptomatic angina within the past 3 months
History of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes). Atrial fibrillation with controlled ventricular response on treatment is not an exclusion
Myocardial infarction < 3 months from study entry
Uncontrolled or symptomatic congestive heart failure
Prior allogeneic HCT
Participants who have a history of hypersensitivity to murine proteins

Exclusion Criteria

Donors for TSC-100 positive for any HLA-A _02 allele would be excluded unless they are HA-1 negative. If donors with any HLA-A_ 02 allele are considered for patients eligible for TSC-100, the donor would undergo HA-1 testing to ensure that the donor is HA-1 negative (40% probability)
Donors for TSC-101 positive for any HLA-A02 allele are excluded regardless of HA- 2 status
Donors who test positive for any of the following: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection, syphilis, West Nile virus through central lab testing. Donors who screen positive for risk of CreutzfeldtJakob disease or Zika virus infection using donor history questionnaires will also be excluded. Donors with evidence of past CMV or EBV infections will be allowed
Related donor residing outside of the United States of America (USA). If the donor screening, testing and leukapheresis can be performed at the same site where the participant is being treated, the donor is considered eligible
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