Acute Myeloid LeukemiaPhase 2NCT05766514
Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Induction
A Phase 2 study testing Cladribine, Cytarabine and Decitabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Florida at 1 site in United States.
Trial summary
This phase II, open-label, randomized trial will compare the efficacy of the novel regimen of cladribine/low-dose cytarabine alternating with decitabine to the current standard of care regimen of hypomethylating agents (decitabine or azacitidine) plus venetoclax in patients with acute myeloid leukemia (AML) or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Cladribine, Cytarabine and Decitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2025to Dec 2030
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 60 years.
- Adults < 60 years are eligible if deemed unfit for intensive induction by their treating physician (or choose to receive a non-intensive regimen due to patient's preference)
- Diagnosis of treatment-naive AML (excluding acute promyelocytic leukemia treated with hydroxyurea) or high grade MDS defined as >10% marrow blasts or R-IPSS of intermediate 2 risk or higher with > 10% bone marrow blasts, and 1 or more of the following:
- Circulating blasts in peripheral blood
- Rapidly declining blood counts over the past 8 weeks, as determined by treating investigator
- Transfusion dependence
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- Adverse cytogenetic changes or molecular mutations with high risk of rapid progression to AML, as determined by treating investigator
- Significant B-symptoms attributed to MDS (weight loss, fatigue, unexplained fever, night sweats)
- Evidence of clonal evolution with emergence of new cytogenetic changes or new mutations compared to previous bone marrow biopsy.
- White blood cell count < 25 K/uL. Cytoreduction with hydroxyurea is allowed prior to enrollment to obtain white blood cell count < 25 K/uL.
- Subjects of childbearing potential (SOCBP) must have a negative pregnancy test and agree to use of an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 months after the last dose of study drug. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.
Who cannot join
- Participants with acute promyelocytic leukemia (APML, APL, AML-M3)
- Patient with active central nervous system leukemia
- Karnofsky performance status < 50 at screening
- Karnofsky performance status of 40-50 is allowed to proceed on study if the patient had a performance status of 50-100 at screening and the decline to 40 is deemed definitely related to disease (AML/MDS).
- Patients with AML with molecular mutations with FDA approved targeted therapies in the first line setting.
- This includes FLT3 ITD/TKD + AML, IDH1+ AML. (Note: IDH2+ AML has targeted therapy approved in relapsed setting only; FDA approval for first line setting is pending and will be excluded once approval is obtained).
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- Subjects with familial AML/MDS syndromes and those with inherited DNA repair syndromes like Fanconi Anemia
- Concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in this clinical study.
- Severe kidney impairment CrCL < 10 mL/min (per Cockcroft Gault equation) or dialysis-depended renal failure
- Class III-IV NYHA heart failure
- Child-Pugh class C liver cirrhosis
- Known seropositivity or active viral infection with human immunodeficiency virus (HIV), hepatis B virus (HBV), or hepatitis C virus (HCV) unless fully treated and negative by PCR. Patients who are seropositive because of HBV vaccine are eligible.
- Subjects with uncontrolled life-threatening infections
- Subjects with fever (temperature > 38.3 C) thought to be related to AML/MDS are eligible
- History of allergic reaction to hypomethylating agents (decitabine, azacitidine), venetoclax, cladribine, or cytarabine.
- Active solid tumor malignancy requiring treatment within previous 2 years.
- Patients with prior history of malignancy who completed treatment > 2 years prior to baseline are eligible to enroll if there is currently no evidence of disease and all toxicities of prior treatments are resolved.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
- Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Prospective Randomized Control Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Induction
This phase II, open-label, randomized trial will compare the efficacy of the novel regimen of cladribine/low-dose cytarabine alternating with decitabine to the current standard of care regimen of hypomethylating agents (decitabine or azacitidine) plus venetoclax in patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome (MDS) who are either elderly or unfit for intensive induction. Subjects will be randomized to be treated with either cladribine/low-dose cytarabine alternating with decitabine (Arm A) or decitabine or azacitadine plus venetoclax (Arm B).
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Being tested
- Cladribine, Cytarabine, Decitabine, azacitidine or decitabine, Venetoclax
- Keywords
- acute myeloid leukemia, myelodysplastic syndrome, AML, MDS, induction therapy, low-dose cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Subjects will be given 5 mg/m2 cladribine intravenously on days 1-5 of cycle 1 and on days 1-3 of cycles 2, 5, 6, 9, 10, 13, 14, 17 and 18.
CytarabineDrug
Subjects will be given 20 mg cytarabine subcutaneously twice daily on days 1-10 of cycles 1, 2, 5, 6, 9, 10, 13, 14, 17 and 18.
DecitabineDrug
Subjects will be given 20 mg/m2 decitabine intravenously on days 1-5 of cycles 3, 4, 7, 8, 11, 12, 15 and 16
azacitidine or decitabineDrug
Subjects will be given either 20 mg/m2 decitabine intravenously on days 1-5 of each cycle or 75 mg/m2 azacitidine intravenously or subcutaneously on days 1-7 of each cycle. The treating physician will determine which drug each subject will receive.
VenetoclaxDrug
Subject will take 400 mg venetoclax orally once daily on days 1-21 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Arm A (investigational arm): cladribine, cytarabine, and decitabine | Experimental | Not described Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Decitabine |
| Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax | Active comparator | Not described Receives: Drug: azacitidine or decitabine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of complete remission
Compare the rate of complete remission (per 2017 European LeukemiaNet criteria for AML response assessment) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 18 months
Secondary outcomes (7)
Time to complete remission
Compare time to complete remission (per 2017 European LeukemiaNet criteria for AML response assessment) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 18 months
Time to minimal residual disease (MRD) negativity
Compare time to MRD negativity (as measured by multicolor flow cytometry per current NCCN guidelines) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 18 months
Overall survival
Compare overall survival (defined as the time from date of randomization until date of death) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 30 months
Overall response rate
Compare overall response rate (defined as the number of patients who achieve either complete or partial remission per 2017 European LeukemiaNet criteria for AML response assessment) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 18 months
Time to overall response
Compare time to overall response in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax. Time to overall response is defined as the time interval from the date of treatment initiation to achievement of overall response.
Measured: 18 months
Rate of MRD negativity
Compare rate of MRD negativity (as measured by multicolor flow cytometry per current NCCN guidelines) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
Measured: 18 months
Event-free survival
Compare event-free survival in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax. Event-free survival is defined as the time from the date of randomization to induction treatment failure, relapse in those with a complete remission after induction, or death from any cause.
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study startApr 2025 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2030 (estimated)
Why it stopped: Study disapproved by internal scientific review committee on re-review; study will no longer move forward
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Crispen, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05766514
- Sponsor's protocol ID
- UF-HEM-011
- Other IDs
- OCR43074, IRB202300983
- Status last verified
- Apr 2025
- First submitted
- 1 Mar 2023
- Last updated
- 22 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Prospective Randomized Control Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Induction
- ClinicalTrials.gov ID
- NCT05766514
- Acronym / sponsor ID
- UF-HEM-011
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- acute myeloid leukemia, myelodysplastic syndrome, AML, MDS, induction therapy, low-dose cytarabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study disapproved by internal scientific review committee on re-review; study will no longer move forward
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Apr 2025 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 13 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II, open-label, randomized trial will compare the efficacy of the novel regimen of cladribine/low-dose cytarabine alternating with decitabine to the current standard of care regimen of hypomethylating agents (decitabine or azacitidine) plus venetoclax in patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome (MDS) who are either elderly or unfit for intensive induction. Subjects will be randomized to be treated with either cladribine/low-dose cytarabine alternating with decitabine (Arm A) or decitabine or azacitadine plus venetoclax (Arm B).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (investigational arm): cladribine, cytarabine, and decitabine | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: Decitabine |
| Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax | Active comparator | Drug: azacitidine or decitabine, Drug: Venetoclax |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age > 60 years.
- Diagnosis of treatment-naive AML (excluding acute promyelocytic leukemia treated with hydroxyurea) or high grade MDS defined as >10% marrow blasts or R-IPSS of intermediate 2 risk or higher with > 10% bone marrow blasts, and 1 or more of the following:
- White blood cell count < 25 K/uL. Cytoreduction with hydroxyurea is allowed prior to enrollment to obtain white blood cell count < 25 K/uL.
- Subjects of childbearing potential (SOCBP) must have a negative pregnancy test and agree to use of an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 months after the last dose of study drug. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.
Key exclusion criteria (19 listed)
- Participants with acute promyelocytic leukemia (APML, APL, AML-M3)
- Patient with active central nervous system leukemia
- Karnofsky performance status < 50 at screening
- Patients with AML with molecular mutations with FDA approved targeted therapies in the first line setting.
- Subjects with familial AML/MDS syndromes and those with inherited DNA repair syndromes like Fanconi Anemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineSubjects will be given 5 mg/m2 cladribine intravenously on days 1-5 of cycle 1 and on days 1-3 of cycles 2, 5, 6, 9, 10, 13, 14, 17 and 18. | Drug | Arm A (investigational arm): cladribine, cytarabine, and decitabine |
| CytarabineSubjects will be given 20 mg cytarabine subcutaneously twice daily on days 1-10 of cycles 1, 2, 5, 6, 9, 10, 13, 14, 17 and 18. | Drug | Arm A (investigational arm): cladribine, cytarabine, and decitabine |
| DecitabineSubjects will be given 20 mg/m2 decitabine intravenously on days 1-5 of cycles 3, 4, 7, 8, 11, 12, 15 and 16 | Drug | Arm A (investigational arm): cladribine, cytarabine, and decitabine |
| azacitidine or decitabineSubjects will be given either 20 mg/m2 decitabine intravenously on days 1-5 of each cycle or 75 mg/m2 azacitidine intravenously or subcutaneously on days 1-7 of each cycle. The treating physician will determine which drug each subject will receive. | Drug | Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax |
| VenetoclaxSubject will take 400 mg venetoclax orally once daily on days 1-21 of each cycle. | Drug | Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax |
Primary outcome
Rate of complete remission
Time frame: 18 months
Compare the rate of complete remission (per 2017 European LeukemiaNet criteria for AML response assessment) in patients treated with cladribine/cytarabine alternating with decitabine to that for patients treated with decitabine or azacitidine and venetoclax
7 secondary outcomes
Time to complete remission
Time frame: 18 months
Time to minimal residual disease (MRD) negativity
Time frame: 18 months
Overall survival
Time frame: 30 months
Overall response rate
Time frame: 18 months
Time to overall response
Time frame: 18 months
Rate of MRD negativity
Time frame: 18 months
Event-free survival
Time frame: 30 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Crispen, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cladribine, Cytarabine and Decitabine in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of complete remission (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2025.