Clinical trial NCT06462365: Prevention of GvHD in Participants With Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplant (HSCT)
Official title: Phase I, First in Human, Open Label Study to Evaluate Safety and Tolerability of TRX103 Cells in Subjects With Hematological Malignancies Undergoing HLA-mismatched Related or Unrelated Hematopoietic Stem Cell Transplantation (HSCT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hematologic Malignancy
GvHD
GVHD,Acute
GVHD, Chronic
Hematopoietic Stem Cell Transplant
Acute Lymphoblastic Leukemia, Adult B-Cell
Acute Lymphoblastic Leukemia, Adult T-Cell
Acute Myeloid Leukemia in Remission
Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia, in Remission
Cancer Remission
Keywords: AML
CMML
Stem Cell Transplant
B-ALL
T-ALL
Acute GvHD
Graft versus Host Disease
Chronic GvHD
MDS
Cellular Therapy
Autoimmune
T regulatory cells
Lead sponsor: Tr1X, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase 1, first in human open-label study is to assess the safety and tolerability of TRX-103 in patients with hematological malignancies undergoing HLA-mismatched related or unrelated hematopoietic stem cell transplantation (HSCT). It is anticipated that up to 36 Subjects will be enrolled during a 18-24 month enrollment period. TRX-103 will be infused one time post HSCT.


Eligibility criteria: Inclusion Criteria:

1. Subjects with one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (B- or T-ALL), Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), or Chronic myelomonocytic leukemia (CMML)
2. Males and Females Age ≥ 18 years.
3. Weight of ≥ 35 Kg.
4. Karnofsky performance status ≥ 70 %.
5. Available mismatched related (haploidentical) or unrelated donors for peripheral blood stem cell (PBSC) donation.
6. Subjects must otherwise fulfill institutional criteria for eligibility to undergo allogeneic stem cell transplantation.
7. Absence of uncontrolled bacterial, viral or fungal infection at time of enrollment.
8. Have adequate organ function.
9. Subjects \> 65-year-old receiving MAC conditioning will only be eligible if they have a HSCT-comorbidity index score \< 5.
10. Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits.

Exclusion Criteria:

1. Prior allogeneic bone marrow, peripheral blood, or cord blood HSCT.
2. Any subject with a history of significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support cardiac dysfunction.
3. HIV positive.
4. Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative.
5. Positive hepatitis-C antibody with positive Recombinant Immunoblot Assay (RIBA) or PCR unless the subject has received curative anti-viral treatment and confirmed negative viral load by PCR.
6. Received another investigational agent for treatment of disease understudy within 28 days (or 5 half-lives, whichever is shorter) of conditioning and/or have not recovered from treatment related toxicities.
7. Subjects with a previous history of Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS) who are not good candidates for treatment with sirolimus.
8. Subjects that are pregnant, breast feeding or aim to become pregnant during the study period. (Subjects must agree to use a highly effective method of contraception).
9. Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results.

Primary outcomes:
measure: Safety and tolerability of TRX103 cell infusion through incidence of Adverse events.
timeFrame: Up to a year
measure: Safety of TRX103 determined by stem cell engraftment and donor chimerism after HSCT measured by absolute neutrophil counts and percent donor chimerism.
timeFrame: Up to day 42
measure: Safety of TRX103 determined by negative Replication Competent Lentivirus (RCL).
timeFrame: At 3-month, 6-month, and 1-year.
Secondary outcomes:
measure: Incidence of Grade II-IV acute GvHD (aGvHD).
timeFrame: Day 0 to Day +100 day
measure: Incidence of Grade III-IV acute GvHD (aGvHD).
timeFrame: Day 0 to Day +100 day
measure: Incidence and severity of chronic GvHD (cGvHD)
timeFrame: Day +100 through Day +365
measure: Overall survival at Day +365.
timeFrame: Up to a year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
affiliation: Tr1X, Inc.
name: Maria Grazia Roncarolo, MD
role: STUDY_DIRECTOR
References: