Preventing Acute GVHD After Stem Cell Transplant

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

This study is testing a new way to give a medication before and during stem cell transplants to see if it can help prevent a serious condition called acute GVHD in patients.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Alabama at Birmingham (other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Birmingham, Alabama)
• Trial ID: NCT06265584 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a two-step dosing regimen of anti-thymocyte globulin (ATG) combined with standard medications to prevent acute graft versus host disease (GVHD) in patients undergoing allogeneic stem cell transplantation. The approach aims to enhance the graft versus leukemia effect while minimizing the risk of severe GVHD by adjusting the timing and dosage of ATG administration. Participants will receive the majority of their ATG dose in the days leading up to the transplant, with a smaller dose given just before the procedure. The study will evaluate the effectiveness of this regimen in improving patient outcomes, particularly in reducing the incidence of severe GVHD and improving overall survival rates.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 who are undergoing allogeneic stem cell transplantation and have a suitable matched donor.

Not a fit: Patients who do not have a compatible stem cell donor or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the incidence of severe acute GVHD, improving survival rates for patients undergoing stem cell transplants.

How similar studies have performed: Preliminary data from similar approaches suggest potential success in preventing severe GVHD, indicating that this method may build on existing knowledge in the field.

Eligibility criteria

Inclusion 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:

    A-AML with either detectable AML on pre AHSCT bone marrow (microscopic ≤5, flow or cytogenetic), or adverse cytogenetic, or molecular features (≥ 4 clonal abnormalities, or monosomal karyotype, inv(3)/t(3;3) or, EV11+, FLT3-ITD (+) without MPN1, P53 mutation positive, ASXL1+, mutant RUNX1.

    B- MDS with the following features: Residual blasts \> 5% blasts in the bone marrow after hypomethylating agents +/- venetoclax, MDS with high IPSS-R and monosomal karyotype, MDS with P-53 or JAK2 mutation.

    C-Myelofibrosis with blasts in the peripheral blood.
12. The subject is willing and able to signed informed consent and abide by the protocol requirements.

Exclusion Criteria:

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.

Where this trial is running

Birmingham, Alabama

• University of Alabama at Birmingham — Birmingham, Alabama, United States (RECRUITING)

Study contacts

• Principal investigator: Zaid Al Kadhimi, MD — The University of Alabama at Birmingham
• Study coordinator: Zaid Al Kadhimi, MD

Conditions: Acute Leukemia, Myelodysplastic Syndrome, Myeloproliferative Disorders, Leukemia, Myeloproliferative