Acute LeukemiaPhase 2NCT06265584
Trial of 2 Step ATG for Prevention of Acute GVHD Post Allogeneic Stem Cell Transplant
A Phase 2 study testing ATG dosing platform when combined with standard tacrolimus and mini methotrexate in people with Acute Leukemia and Myelodysplastic Syndrome, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Leukemia, Myelodysplastic Syndrome, Myeloproliferative Disorders
- What is being tested?
- ATG dosing platform when combined with standard tacrolimus and mini methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2025to Nov 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female, age 18-75 years
- 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.
- 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.
- Cardiac function: Ejection fraction >40%
- Measured creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
- Pulmonary function: DLCO ≥50% (adjusted for hemoglobin) and FEV1≥50%
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- 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.
- 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.
- 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.
- Karnofsky performance status KPS ≥ 70
- 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.
- The subject is willing and able to signed informed consent and abide by the protocol requirements.
Who cannot join
- Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
- Patients with florid residual AML with > 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study.
- Previous allogeneic stem cell transplant.
- Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
- Known hypersensitivity to one or more of the study agents
- Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
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- Pregnant and/or breastfeeding
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Patient with documented cirrhosis
- 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
- Participation in another clinical study with an investigational product during the last 28 days.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Margaret Thomas, MPH contact
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Zaid Al Kadhimi, MD, (205) 975-1269, zsalkadhimi@uabmc.edu
Zaid Al Kadhimi, MD
About this study
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
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.
- Being tested
- ATG dosing platform when combined with standard tacrolimus and mini methotrexate
- Keywords
- Leukemia, Myelodysplastic Syndrome, Myeloproliferative
- Medical subject headings
- Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATG dosing platform when combined with standard tacrolimus and mini methotrexateDrug
On Day -8, you will be admitted to the hospital and receive a dose of prednisone at 1 mg/kg (ATG premedication). You will receive a steroids 3 hours before every ATG infusion. On day -7, you will receive a small dose of ATG as an intravenous (IV) infusion. ATG will be repeated on days -6, -5 and -1. Routine transplant chemotherapy agent fludarabine will be given on days -7 to -3 as daily IV infusions. Melphalan, another routine transplant chemotherapy will be given on day -4 as IV infusion. Tacrolimus (standard immune suppression agent) will start on day -3 as continuous IV infusion and switched to oral after engraftment. Methotrexate is another standard immune suppression medication which is given IV on day +1, +3, +6, and +11 post-transplant. We plan to draw blood on days -4,, -1, +3, +7, and +14 to measure ATG levels.
| Study group | Role | What they receive |
|---|---|---|
| phase II single arm study of 2 step ATG dosing in prevention of aGVHD | Experimental | The primary outcome for the study is GRFS rate at one-year post transplant. GRFS will be estimated using Kaplan Meier method The reported GRFS with recent phase III trial of PTCY/tac/MMF in transplant from matched related and unrelated donors at 1 year follow up was 52%. We hypothesize that with 2 step ATG/Tac/Mini MTX regimen, we can achieve a one year GRFS of 69%. Receives: Drug: ATG dosing platform when combined with standard tacrolimus and mini methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of GRFS (graft versus host disease GVHD, relapse free survival) at one year post transplant.
Rate of GRFS is defined as the time from date of first dose of fludarabine until occurrence of grade III-IV aGVHD, and or cGVHD requiring systemic immune suppression, and or disease progression or death whichever comes first.
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start8 Apr 2025
- Primary completionAug 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zaid Al-Kadhimi, University of Alabama at Birmingham
- Investigators
- Zaid Al Kadhimi, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06265584
- Sponsor's protocol ID
- IRB-300011730 (UAB2370)
- Other IDs
- Robert Award
- Status last verified
- Oct 2025
- First submitted
- 5 Feb 2024
- Last updated
- 8 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No