Relapsed or Refractory Acute Myeloid Leukemia (AML)Phase 2NCT06660368
BCL2i CLAG-M in R/R Acute Myeloid Leukemia
A Phase 2 study testing Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen and Venetoclax in people with Relapsed or Refractory Acute Myeloid Leukemia (AML), run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites in United States.
Trial summary
This multicenter, open-label phase II study combines CLAG-based therapy with or without venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) in order to improve measurable residual disease (MRD) clearance and event-free survival. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Relapsed or Refractory Acute Myeloid Leukemia (AML)
- What is being tested?
- Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen 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
- 52 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Nov 2024to Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form.
- Ability to understand and stated willingness to comply with all study procedures and availability for the duration of the study.
- Adults aged ≥18 years - 80 years.
- Patients with documented refractory or relapsed AML: Refractory disease is defined as failure to achieve CR (i.e., <5% blasts in BM or blood) with or without normal restoration of hematopoiesis (Cri) after at least 1 cycle of intensive induction therapy (or 2 cycles of non-intensive induction). Relapse: Recurrence of disease after achieving remission, meeting one or more of the following criteria: ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease.
- Secondary AML arising out of MDS previously treated with HMA, HMA + venetoclax (if > 3 months from venetoclax exposure), and/or 1 cycle of induction chemotherapy.
- Extramedullary AML with marrow involvement is allowed as long as concurrent medullary AML is present.
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- ECOG performance status ≤ 2.
- Participants must have adequate organ function as defined within the protocol.
- Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not mandatory.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and have an undetectable HCV viral load. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Testing is not mandatory.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 4 months after completion of study drug administration.
Who cannot join
- Venetoclax-refractory disease or recent venetoclax exposure < 3 months prior to first dose of study therapy.
- Prior treatment with a high-dose cytarabine-containing regimen (e.g., no prior CLAG/FLAG/MEC/CLIA/HAM, etc.).
- Allogeneic stem cell transplant in the past 3 months.
- Less than 14 days from last AML-directed therapy or five half-lives, whichever is shorter, not including hydroxyurea.
- Known history of prior TP53 mutation (results from any myeloid mutation panel are not required for screening eligibility).
- Active CNS involvement by AML.
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- WBC count ≥25k at the time study treatment begins.
- Uncontrolled intercurrent systemic illness that would limit compliance.
- Concurrent malignancy in addition to AML that requires active treatment with some exceptions.
- Immunosuppressive therapy in the past 14 days except for prednisone at ≤ 10 mg/day or equivalent AND no active or uncontrolled graft-versus-host disease (GvHD).
- Participants who have not recovered from adverse events (Aes) due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1), with the exception of alopecia.
- Participants who are receiving any other investigational agents.
- Participants with psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with active heart disease that limits the use of mitoxantrone or recent (<6 months) history of an acute cardiovascular event (STEMI, NSTEMI).
- Pregnant women are excluded from this study because venetoclax, cladribine, and cytarabine are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Jacqueline Garcia, MD, 617-632-1906, jacqueline_garcia@dfci.harvard.edu
Jacqueline Garcia, MD
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
David Sallman, MD
Onyee Chan, MD
About this study
Official title: A Prospective, Multicenter, Randomized, Open-Label, Phase II Study of Salvage BCL2i Plus CLAG-M in Relapsed or Refractory Acute Myeloid Leukemia
This multicenter, open-label phase II study combines CLAG-based therapy with or without venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) in order to improve measurable residual disease (MRD) clearance and event-free survival. Investigators hypothesize that the addition of venetoclax to CLAG-M in patients with relapsed or refractory AML is safe, and superior to CLAG-M alone in improving patient outcomes.
- Being tested
- Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen, Venetoclax
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimenDrug
Filgrastim/G-CSF 300 mcg/day for 6 days beginning 24 hours prior to multiagent chemotherapy (days 0-5), cladribine 5 mg/m2 given intravenously over 2 hours for 5 consecutive days (days 1-5), cytarabine given IV over 4 hours for 5 consecutive days (days 1-5) beginning 2 hours after the completion of cladribine, and mitoxantrone 16 mg/m2 given intravenously over 30 minutes for 3 days (days 1-3) after completion of cytarabine.
VenetoclaxDrug
Venetoclax will be administered orally, once daily, with food.
| Study group | Role | What they receive |
|---|---|---|
| CLAG-based therapy with venetoclax | Experimental | Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) and Venetoclax Receives: Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen; Drug: Venetoclax |
| CLAG-based therapy without venetoclax | Active comparator | Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) Receives: Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRD-Negative Remission Rate
The rate of MRD negative remission will be calculated for each arm.
Measured: Up to 18 months
Secondary outcomes (3)
Event-free survival (EFS)
EFS will be measured from the date of randomization to the first of:
failure to achieve composite CR by the end of induction, relapse after achieving composite CR, or death from any cause
Measured: Up to 18 months
Treatment-Related Toxicities
The number of participants who experience an AE or SAE.
Measured: Up to 18 months
Overall survival (OS) based on treatment arm
OS is defined as time from treatment initiation to death or last follow-up if alive at last follow-up.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2024
- Study start26 Nov 2024
- Primary completionNov 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- 52 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor
- Investigators
- David Sallman, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06660368
- Sponsor's protocol ID
- MCC-23154
- Status last verified
- Mar 2026
- First submitted
- 24 Oct 2024
- Last updated
- 1 Apr 2026
- 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 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Randomized, Open-Label, Phase II Study of Salvage BCL2i Plus CLAG-M in Relapsed or Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06660368
- Acronym / sponsor ID
- MCC-23154
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- 26 Nov 2024 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 28 Oct 2024 (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 multicenter, open-label phase II study combines CLAG-based therapy with or without venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) in order to improve measurable residual disease (MRD) clearance and event-free survival. Investigators hypothesize that the addition of venetoclax to CLAG-M in patients with relapsed or refractory AML is safe, and superior to CLAG-M alone in improving patient outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLAG-based therapy with venetoclax | Experimental | Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen, Drug: VenetoclaxStudy participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) and Venetoclax |
| CLAG-based therapy without venetoclax | Active comparator | Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimenStudy participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provision of signed and dated informed consent form.
- Ability to understand and stated willingness to comply with all study procedures and availability for the duration of the study.
- Adults aged ≥18 years - 80 years.
- Patients with documented refractory or relapsed AML: Refractory disease is defined as failure to achieve CR (i.e., <5% blasts in BM or blood) with or without normal restoration of hematopoiesis (Cri) after at least 1 cycle of intensive induction therapy (or 2 cycles of non-intensive induction). Relapse: Recurrence of disease after achieving remission, meeting one or more of the following criteria: ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease.
- Secondary AML arising out of MDS previously treated with HMA, HMA + venetoclax (if > 3 months from venetoclax exposure), and/or 1 cycle of induction chemotherapy.
Key exclusion criteria (15 listed)
- Venetoclax-refractory disease or recent venetoclax exposure < 3 months prior to first dose of study therapy.
- Prior treatment with a high-dose cytarabine-containing regimen (e.g., no prior CLAG/FLAG/MEC/CLIA/HAM, etc.).
- Allogeneic stem cell transplant in the past 3 months.
- Less than 14 days from last AML-directed therapy or five half-lives, whichever is shorter, not including hydroxyurea.
- Known history of prior TP53 mutation (results from any myeloid mutation panel are not required for screening eligibility).
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 |
|---|---|---|
| Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimenFilgrastim/G-CSF 300 mcg/day for 6 days beginning 24 hours prior to multiagent chemotherapy (days 0-5), cladribine 5 mg/m2 given intravenously over 2 hours for 5 consecutive days (days 1-5), cytarabine given IV over 4 hours for 5 consecutive days (days 1-5) beginning 2 hours after the completion of cladribine, and mitoxantrone 16 mg/m2 given intravenously over 30 minutes for 3 days (days 1-3) after completion of cytarabine. | Drug | CLAG-based therapy with venetoclax, CLAG-based therapy without venetoclax |
| VenetoclaxVenetoclax will be administered orally, once daily, with food. | Drug | CLAG-based therapy with venetoclax |
Primary outcome
MRD-Negative Remission Rate
Time frame: Up to 18 months
The rate of MRD negative remission will be calculated for each arm.
3 secondary outcomes
Event-free survival (EFS)
Time frame: Up to 18 months
Treatment-Related Toxicities
Time frame: Up to 18 months
Overall survival (OS) based on treatment arm
Time frame: Up to 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
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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.
David Sallman, MD principal investigator
Moffitt Cancer Center
2 sites 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, Mitoxantrone, G-CSF (CLAG-M) regimen and Venetoclax in people with Relapsed or Refractory Acute Myeloid Leukemia (AML), run by H. Lee Moffitt Cancer Center and Research Institute at 2 sites 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 12 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Quan Lovette (813-745-4194, quan.lovette@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRD-Negative Remission Rate (time frame: Up to 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 1 Apr 2026.