RECRUITING

Trial of 2 Step ATG for Prevention of Acute GVHD Post Allogeneic Stem Cell Transplant

Conditions

Acute Leukemia Myelodysplastic Syndrome Myeloproliferative Disorders Leukemia Myeloproliferative

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

In an effort to reduce graft versus host disease (GVHD) and enhance graft versus leukemia (GVL) effect post allogenic hematopoietic stem cell transplantation (AHSCT), recent research has focused on host immune cell depletion. Frame shifting anti-thymocyte globulin (ATG) backwards to earlier days before days 0 can result in deeper host and less graft T-cell depletion, leading to better immune reconstitution. Preliminary data where 80% of the ATG dose is given on days -6,-5,-4 and 20% given on day -1, showed effective prevention of severe acute GVHD, chronic GVHD and favorable early immune reconstitution. We hypothesize that our 2 step ATG dosing platform when combined with standard tacrolimus and mini methotrexate can prevent grade III-IV acute GVHD and chronic GVHD, resulting in improvement of GVHD/relapse free survival at one year post transplant.

Official Title

Phase II Clinical Trial of 2 Step ATG Combined With Tacrolimus and Mini Methotrexate for Prevention of Acute GVHD Post Reduced Intensity Allogeneic Stem Cell Transplant

Quick Facts

Study Start:2025-04-08

Study Completion:2028-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06265584

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Adult male or female, age 18-75 years 2. Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to NMDP criteria. 3. A candidate for reduced intensity preparative regimen, based on age≥60, or HCT-CI of ≥4, or considered by the treating physician to have high risk for toxicity with myeloablative preparative regimen. 4. Cardiac function: Ejection fraction \>40% 5. Measured creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight) 6. Pulmonary function: DLCO ≥50% (adjusted for hemoglobin) and FEV1≥50% 7. Liver function: total bilirubin \< 1.5x the upper limit of normal and ALT/AST \< 2.5x the upper normal limit. Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of up to \<3mg/dl. 8. Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception or agree to complete abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant. 9. Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant. 10. Karnofsky performance status KPS ≥ 70 11. Patients must have a diagnosis of one of the following: 12. The subject is willing and able to signed informed consent and abide by the protocol requirements.	1. Autologous hematopoietic stem cell transplant \< 3 months prior to enrollment. 2. Patients with florid residual AML with \> 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study. 3. Previous allogeneic stem cell transplant. 4. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities. 5. Known hypersensitivity to one or more of the study agents 6. Received any investigational drugs within the 14 days prior to the first day of transplant conditioning 7. Pregnant and/or breastfeeding 8. Evidence of HIV infection or known HIV positive serology. 9. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). 10. Patient with documented cirrhosis 11. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma. Patients with prior malignancies except resected localized non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously must be reviewed and approved by the PI 12. Participation in another clinical study with an investigational product during the last 28 days.

Inclusion Criteria

Exclusion Criteria

1. Adult male or female, age 18-75 years
2. Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to NMDP criteria.
3. A candidate for reduced intensity preparative regimen, based on age≥60, or HCT-CI of ≥4, or considered by the treating physician to have high risk for toxicity with myeloablative preparative regimen.
4. Cardiac function: Ejection fraction \>40%
5. Measured creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
6. Pulmonary function: DLCO ≥50% (adjusted for hemoglobin) and FEV1≥50%
7. Liver function: total bilirubin \< 1.5x the upper limit of normal and ALT/AST \< 2.5x the upper normal limit. Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of up to \<3mg/dl.
8. Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception or agree to complete abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.
9. Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant.
10. Karnofsky performance status KPS ≥ 70
11. Patients must have a diagnosis of one of the following:
12. The subject is willing and able to signed informed consent and abide by the protocol requirements.

1. Autologous hematopoietic stem cell transplant \< 3 months prior to enrollment.
2. Patients with florid residual AML with \> 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study.
3. Previous allogeneic stem cell transplant.
4. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
5. Known hypersensitivity to one or more of the study agents
6. Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
7. Pregnant and/or breastfeeding
8. Evidence of HIV infection or known HIV positive serology.
9. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
10. Patient with documented cirrhosis
11. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma. Patients with prior malignancies except resected localized non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously must be reviewed and approved by the PI
12. Participation in another clinical study with an investigational product during the last 28 days.

Contacts and Locations

Study Contact

Razan Mohty, MD

CONTACT

205-934-5865

rmohty@uabmc.edu

Margaret Thomas, MPH

CONTACT

margaretannthomas@uabmc.edu

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-08

Study Completion Date2028-11

Study Record Updates

Study Start Date2025-04-08

Study Completion Date2028-11

Terms related to this study

Keywords Provided by Researchers

Leukemia
Myelodysplastic Syndrome
Myeloproliferative

Additional Relevant MeSH Terms

Acute Leukemia
Myelodysplastic Syndrome
Myeloproliferative Disorders