Acute Lymphoblastic Leukemia, Adult B-Cell, Acute Lymphoblastic Leukemia, Adult T-Cell, Acute Myeloid Leukemia in Remission, Cancer Remission, Chronic Myelomonocytic Leukemia, in Remission, GvHD, GVHD,Acute, GVHD, Chronic, Hematologic Malignancy, Hematopoietic Stem Cell Transplant, Myelodysplastic Syndromes
Conditions
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
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.
Interventions
BIOLOGICALTRX103
TRX103 infusion via central line.
Sponsors
Tr1X, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of TRX103 cell infusion through incidence of Adverse events. | Up to a year |
| Safety of TRX103 determined by stem cell engraftment and donor chimerism after HSCT measured by absolute neutrophil counts and percent donor chimerism. | Up to day 42 |
| Safety of TRX103 determined by negative Replication Competent Lentivirus (RCL). | At 3-month, 6-month, and 1-year. |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of Grade II-IV acute GvHD (aGvHD). | Day 0 to Day +100 day |
| Overall survival at Day +365. | Up to a year |
| Incidence of Grade III-IV acute GvHD (aGvHD). | Day 0 to Day +100 day |
| Incidence and severity of chronic GvHD (cGvHD) | Day +100 through Day +365 |
Countries
United States
Contacts
Primary ContactTr1X Clinical Trials
Outcome results
None listed