Myeloid MalignancyPhase 1NCT07044544
Trial of Novel Anti-leukemia Agents in Flu/Mel RIC Transplant for Myeloid Malignancies
A Phase 1 study testing G-CSF, Decitabine and Venetoclax in people with Myeloid Malignancy and Hematologic Malignancy, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety of adding Decitabine and Venetoclax to patients undergoing reduced intensity allogenic transplantation for treatment of hematologic malignances with Fludarabine and Melphalan. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Myeloid Malignancy, Hematologic Malignancy, Acute Myeloid Leukemia
- What is being tested?
- G-CSF, Decitabine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2025to Jan 2027
- Phase
- Phase 1
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 the following: have Optimum: HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1; Minimum: HLA-A, -B, -C, -and DRB1 matching at high resolution using DNA-based typing and be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to National Marrow Donor Program (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%
- Calculated 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 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 (Appendix B)
- Patients must have a diagnosis of one of the following:
- -AML: A. Any AML with active disease (defined as ≥ 5% blasts in the marrow), with no available re-induction strategies, or further therapy is not felt to be effective by treating physician.
- Any AML with adverse risk disease, therapy-related or secondary-AML in CR1 or beyond C. AML with intermediate risk disease that is MRD+ in CR1 or beyond D. Any AML in CR2 or beyond (regardless of MRD) E. Marrow blast percentage needs to be 20-25% and total WBC counts needs to be ≤ 25000/µl before the start of the conditioning regimen. It is acceptable to use hydroxyurea or low dose cytarabine to maintain this WBC count.
- -MDS:
- MDS with IPSS-M ≥ high and/or with ≥5% blasts in the bone marrow with no available pre-transplant strategies, or further therapy is not felt to be effective by treating physician.- MDS/MPN:
- -MDS/MPN >5% blasts and spleen < 22 cm with no available pre-transplant strategies, or further therapy is not felt to be effective by treating physician.
- Subject is willing and able to sign informed consent and abide by the protocol requirements.
Who cannot join
- Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
- 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 Decitabine, Venetoclax and/or ATG.)
- Pregnant and/or breastfeeding
- Evidence of HIV infection or known HIV positive serology.
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- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- 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 as long as it is in remission. Cancer treated with curative intent < 5 years previously must be reviewed and approved by the PI as long as it is in remission.
- Participation in another clinical study with an investigational product during the last 28 days.
- Patients with documented cirrhosis (will need imaging +/- biopsy confirmation, hepatology consult recommended)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Margaret A Thomas, MPH contact
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Margaret Thomas, MPH, margaretannthomas@uabmc.edu
Zaid Al-Kadhimi, MD
About this study
Official title: A Phase I Trial to Evaluate the Safety and Efficacy of Addition of Novel Anti-leukemia Agents to Flu/Mel RIC Transplant for High-risk Myeloid Malignancies
The purpose of this study is to determine the safety of adding Decitabine and Venetoclax to patients undergoing reduced intensity allogenic transplantation for treatment of hematologic malignances with Fludarabine and Melphalan.
Read the detailed description
The purpose of this study is to evaluate the safety, tolerability and preliminary activity of decitabine and venetoclax as part of RIC AHSCT in patients with high-risk AML and MDS. The study will follow a standard 3+3 design commonly used in phase I studies. Dose-adjustments will be made based on the incidence of dose-limiting toxicities (DLTs). The DLT period is from the first dose of decitabine to day 28 post-transplant.
Cohort 1 DL1: G-CSF + Decitabine (100mg/m2 bid for 2d) Cohort 1 DL-1: G-CSF + Decitabine (50mg/m2 bid for 2d) Cohort 2 DL1: G-CSF + Decitabine + Ven (200mg/d for 7d) Cohort 2 DL2: G-CSF + Decitabine + Ven (400mg/d for 7d)
- Conditions
- Myeloid Malignancy, Hematologic Malignancy, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- G-CSF, Decitabine, Venetoclax
- Keywords
- Leukemia, allogeneic transplant
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
G-CSFDrug
Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
DecitabineDrug
Also called Dacogen
Decitabine is a hypomethylating agent.
VenetoclaxDrug
Venetoclax is a selective inhibitor of BCL-2 protein.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: G-CSF + Decitabine (100mg/m2 bid for 2d) | Experimental | Cohort 1 DL1: G-CSF + Decitabine (100mg/m2 bid for 2d)
G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc >20k.
Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10. Receives: Drug: G-CSF; Drug: Decitabine |
| Cohort 1 DL-1: G-CSF + Decitabine (50mg/m2 bid for 2d) | Experimental | Cohort 1 DL-1: G-CSF + Decitabine (50mg/m2 bid for 2d)
G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc >20k.
Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10. Receives: Drug: G-CSF; Drug: Decitabine |
| Cohort 2: G-CSF + Decitabine + Ven (200mg/d for 7d) | Experimental | Cohort 2 DL1: G-CSF + Decitabine + Ven (200mg/d for 7d)
G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc >20k.
Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10.
Venetoclax will be investigated at two dose levels. 200mg daily for 7 days as dose level 1 of cohort 2 of the study and 400mg daily for 7 days as dose level 2. It will be administered orally on from days -12 to -6.
Venetoclax 400 and 200 mg/day dose will be adjusted if the patient was on fluconazole (down to 200 and 100 mg/day), posaconazole or isavuconazole (100 and 50 mg/day), and voriconazole (50 and 25 mg/day)
If cohort 2 DL1 clears the DLT period based on the criteria discussed previously, then we will start accruing patients to DL2 of cohort 2. Receives: Drug: G-CSF; Drug: Decitabine; Drug: Venetoclax |
| Cohort 2 DL2: G-CSF + Decitabine + Ven (400mg/d for 7d) | Experimental | Cohort 2 DL2: G-CSF + Decitabine + Ven (400mg/d for 7d)
G-CSF will be administered subcutaneously on days -14 to -10 at a dose of 5mcg/kg. Hold for wbc >20k.
Decitabine will be investigated at two dose levels. 100mg/m2 bid for 2 days at dose level 1 and 50mg/m2 bid for 2 days at dose level -1. It will be administered as IV in days -11 and -10.
Venetoclax will be investigated at two dose levels. 200mg daily for 7 days as dose level 1 of cohort 2 of the study and 400mg daily for 7 days as dose level 2. It will be administered orally on from days -12 to -6.
Venetoclax 400 and 200 mg/day dose will be adjusted if the patient was on fluconazole (down to 200 and 100 mg/day), posaconazole or isavuconazole (100 and 50 mg/day), and voriconazole (50 and 25 mg/day) Receives: Drug: G-CSF; Drug: Decitabine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring changes in dose limiting toxicities
Determine the safety of adding Decitabine and Venetoclax to patients undergoing reduced intensity allogeneic transplantation for treatment of hematologic malignances with Fludarabine and Melphalan.
Measured: Up to 28 days
Secondary outcomes (1)
The average regimen-related toxicity
Rate of grade >- 4, non-hematologic toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Measured: At 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2025
- Study start17 Jul 2025
- Primary completionDec 2026 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid MalignancyStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Omer Jamy, University of Alabama at Birmingham
- Investigators
- Omer A Jamy, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07044544
- Sponsor's protocol ID
- IRB-300014728 (UAB 2469)
- Other IDs
- Robert Award
- Status last verified
- Mar 2026
- First submitted
- 23 Jun 2025
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No