BCL2i CLAG-M in R/R Acute Myeloid Leukemia

March 31, 2026 updated by: H. Lee Moffitt Cancer Center and Research Institute

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Sub-Investigator:
          • Rami Komrokji, MD
        • Sub-Investigator:
          • Eric Padron, MD
        • Sub-Investigator:
          • Jeffrey Lancet, MD
        • Sub-Investigator:
          • Alison Walker, MD
        • Sub-Investigator:
          • Onyee Chan, MD
        • Principal Investigator:
          • David Sallman, MD
        • Sub-Investigator:
          • Timothy Kubal, MD
        • Sub-Investigator:
          • Zoey Xie, MD
        • Sub-Investigator:
          • Seongseok Yun, MD, PhD
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana-Farber Cancer Institute
        • Contact:
        • Principal Investigator:
          • Jacqueline Garcia, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CLAG-based therapy with venetoclax
Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) and Venetoclax
Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen
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.
Drug: Venetoclax
Venetoclax will be administered orally, once daily, with food.
Active Comparator: CLAG-based therapy without venetoclax
Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone)
Drug: Cladribine, Cytarabine, Mitoxantrone, G-CSF (CLAG-M) regimen
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
MRD-Negative Remission Rate
Time Frame: Up to 18 months
The rate of MRD negative remission will be calculated for each arm.
Up to 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: Up to 18 months

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
Up to 18 months
Treatment-Related Toxicities
Time Frame: Up to 18 months
The number of participants who experience an AE or SAE.
Up to 18 months
Overall survival (OS) based on treatment arm
Time Frame: Up to 18 months
OS is defined as time from treatment initiation to death or last follow-up if alive at last follow-up.
Up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
H. Lee Moffitt Cancer Center and Research Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AbbVie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: David Sallman, MD, Moffitt Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 26, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 28, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MCC-23154

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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