A Study of TSC-100 and TSC-101 in AML, ALL and MDS Patients Undergoing Haploidentical Donor Transplantation
Cancer-Related Syndrome
Leukemia
Myelodysplastic Syndromes (MDS)
18 Years and older, Male and Female
TSCAN-001 (primary)
NCI-2022-06900
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.
Objectives
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.
Eligibility
- Male or female aged = 18 years at the time of signing the informed consent.
- Eastern Cooperative Oncology Group (ECOG)-PS = 2 at the time of the screening visit.
- Contraceptive use by male and female participants must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Male Participants:
- A male participant must agree to use a highly effective contraceptive as detailed in Appendix 4 of this protocol during the intervention period and for at least 12 months after the last dose of study intervention and refrain from donating sperm during this period.
- Female Participants:
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 12 months after the last dose of study intervention.
- Preparing to undergo allogeneic HCT for either of the following:
- AML
- MDS
- ALL
- Participants in the treatment arms must express HLA-A*0201. Participants in the control arm may express any HLA type.
- Having the HA1+/- or HA-1+/+ (HA-1 positive) genotype to be eligible for TSC-100 treatment.
- Having the HA2+/- HA-2+/+ (HA-2 positive) genotype to be eligible for TSC-101 treatment.
- Having a haploidentical related adult donor for HCT who is adequately HLA-matched by institutional standards and meets the donor inclusion criteria.
- Considered to be clinically indicated for haploidentical donor transplantation at the discretion of the treating investigator.
- Considered to be clinically indicated for RIC at the discretion of the treating investigator.
- Considered to be clinically indicated for peripheral blood stem cell transplantation at the discretion of the treating investigator.
- Organ function parameters for transplant eligibility are met per institutional standards.
- Capable of giving signed informed consent - which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Participants must provide consent for mandatory study procedures including bone marrow biopsy and blood sampling for research analyses in the ICF.
- Participants must agree to participate in long-term follow-up for up to 15 years post initial product treatment if they are enrolled in the study and receive the investigational Tcell infusion. Donor Inclusion Criteria :
- Male or female aged = 18 years at the time of signing the informed consent.
- Able to undergo peripheral blood stem cell (PBSC) collection and up to 2 rounds of leukapheresis (for TSC-100 or TSC101 manufacturing for treatment arms only, and f for stem cell collection for both treatment arms and the control arm).
- Donors matched to TSC-100 participants should be HA-1-/- (negative) and/or negative for all HLA-A*02 alleles
- Donors matched to TSC-101 participants should be negative for all HLA-A*02 alleles
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Treatment Sites in Georgia
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