Secondary Acute Myeloid LeukemiaPhase 2NCT05780879

A Proof of Concept Pilot Study of the Addition of Venetoclax to Standard Remission Induction Chemotherapy Fludarabine or Cladrabine, Cytarabine, and Granulocyte Colony Stimulating Factor (G-CSF) (FLAG or CLAG) for Frontline Therapy of Secondary Acute Myeloid Leukemia

A Phase 2 study testing Venetoclax and FLAG or CLAG Protocol in people with Secondary Acute Myeloid Leukemia, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary purpose of this study is to determine complete remission rate of a novel combination induction chemotherapy treatment based upon 20 patients with newly diagnosed secondary AML. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Secondary Acute Myeloid Leukemia
What is being tested?: Venetoclax and FLAG or CLAG Protocol
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteUnited States
Study dates: 3 Jun 2024to 16 Aug 2025
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

Patients have an established, pathologically confirmed diagnosis of newly diagnosed secondary acute myeloid leukemia (sAML) as defined by the 2016 World Health Organization criteria. Secondary AML includes:
AML arising after an antecedent hematologic neoplasm including aplastic anemia (AA), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and overlap syndromes (MDS/MPN)
AML with MDS defining cytogenetic changes as defined in Vardiman et al. Blood 2009 114 (5): 937-951 - Table 6. Please see appendix 14.6 for full table.
Therapy-related AML
Patients must not have received prior treatment for the diagnosis of secondary acute myeloid leukemia, with the exception of hydroxyurea and/or leukopheresis which are permitted until day 1 of study participation. Prior treatment for a diagnosis of MDS, MPN, or MDS/MPN overlap syndrome is allowed.
Patients ≥ 18 years of age.

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ECOG PS ≤ 2
Patient has ability to understand and the willingness to sign a written informed consent.
Adequate organ function as defined by:
serum creatinine level ≤ 2.0 mg/dL or a CrCl ≥ 30 ml/min (Cockcroft-Gault equation using actual body weight)
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 3 times the institutional upper limit of normal (ULN) unless considered due to leukemic involvement
total bilirubin level ≤1.5 times the institutional upper limits of normal (ULN) (unless secondary to Gilbert syndrome, hemolysis, or suspected leukemic involvement).
Patients must be non-fertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate during and for at least 6 months after completion of study therapy.
Patients must be able to comply with the requirements for the entire duration of the study.

Who cannot join

Diagnosed with acute promyelocytic leukemia (acute leukemia with recurrent genetic abnormalities - APL with t(15;17)(q22;q12);PML-RARA).
Diagnosed with myeloid blast phase of chronic myeloid leukemia.
Diagnosed with isolated extramedullary AML
Diagnosed with acute leukemia of ambiguous lineage, acute biphenotypic or acute bilineal acute leukemia per the 2016 World Health Organization classification system.
Patients with a white blood cell count (WBC) >50,000 at the time of initiation of therapy will be excluded. Patients can consent and screen with a WBC > 50,000 but will require cytoreduction (hydrea or leukopheresis) prior to day 1 of therapy.
Receiving antileukemic therapy other than hydroxyurea. Patients may have received therapy with a hypomethylating agent (azacitidine or decitabine) for a prior diagnosis of myelodysplastic syndrome (MDS) or chemotherapy for a prior diagnosis of a myeloproliferative neoplasm or an MDS/MPN overlap syndrome. Likewise, patients may have received chemotherapy for a prior non-leukemic oncologic malignancy.

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Any prior therapy with a Bcl-2 antagonist.
Any known allergy to the chemotherapeutic agents being investigated including fludarabine,cladribine, cytarabine, G-CSF and venetoclax.
Clinical signs of active leptomeningeal leukemia or biopsy proven active leptomeingeal leukemia. A clinical history of previously treated leptomeningeal process is not exclusionary.
Patients with known history of HIV, Hepatitis B, or Hepatitis C with the exception of those with an undetectable viral load within 3 months of screening. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
Having an active second malignancy requiring treatment--other than AML--within 3 months prior to the start of treatment, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin, colon polyp, carcinoma in situ of the cervix, or DCIS/LCIS of the breast.
Having an active uncontrolled infection (viral, bacterial or fungal), any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator.
Pregnant women or women who are breastfeeding. Women must be willing to not breast feed up until 30 days following the end of trial therapy.
Men or women of childbearing potential must be willing to practice an effective method of birth control during treatment and up until 6 months following the end of trial therapy.
Having received any live vaccines within 28 days prior to first study drug administration.
Patient has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
Patient has a cardiovascular disability status of New York Heart Association Class > 2.
Patient has a chronic respiratory disease that requires continuous supplemental oxygen.
Patient has a malabsorption syndrome or other condition that precludes enteral route of administration of medications.
Female subject that has positive results for a screening pregnancy test.
Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception defined as:
Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Female sterilization (surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
Male sterilization (at least six months prior to enrolling). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.
Use of a combination of any two of the following:
Use of oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormonal vaginal ring or transdermal hormone contraception.
Placement of an intrauterine device (IUD) or intrauterine system (IUS).
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/vaginal suppository.
Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
If a study patient becomes pregnant or suspects being pregnant during the study or within 30 days after the final dose of trial therapy, the Study Doctor needs to be informed immediately.
Malabsorption syndrome or other condition that would interfere with enteral absorption or an inability to take oral medications as prescribed.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

The primary purpose of this study is to determine complete remission rate of a novel combination induction chemotherapy treatment based upon 20 patients with newly diagnosed secondary AML.

Conditions: Secondary Acute Myeloid Leukemia
Being tested: Venetoclax, FLAG or CLAG Protocol

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VenetoclaxDrug
Venetoclax administered orally once daily on days 3-16.
FLAG or CLAG ProtocolDrug
FLAG consists of daily infusions of Fludarabine (30mg/m2/day over 30 minutes) and Ara-C (2g/m2/day over 4 hours) for 5 days with daily subcutaneous injections of G-CSF until count recovery. Tbo-filgrastim will be administered as follows: WBC count >50,000 - 5mcg/kg; WBC count <50,000 - hold Tbo-filgrastim. Given the national shortage of Fludarabine, Cladrabine (5mg/m2/day IV over 2 hours) has been substituted (CLAG) with similar toxicity profile.

Study groups in NCT05780879
Study group	Role	What they receive
Venetoclax + FLAG or CLAG induction chemotherapy	Experimental	Induction chemotherapy with FLAG starting on day 1 and venetoclax given on days 3-16. The G-CSF component of FLAG will continue until count recovery (ANC at least > 1000). FLAG dosing will be standard and uniform for all patients and venetoclax dosing will be determined according to institutional guidelines based on the prophylactic antifungal therapy chosen for use during induction therapy. Given the national shortage of Fludarabine, Cladrabine (5mg/m2/day IV over 2 hours) has been substituted (CLAG) with similar toxicity profile. Receives: Drug: Venetoclax; Drug: FLAG or CLAG Protocol

What is being measured

The primary outcome is the main question the study is designed to answer.

Morphologic complete remission (CR)
If at least 12/20 (60%) of patients achieve a CR (based upon a bone marrow aspiration, biopsy, and peripheral blood studies according to the International Working Group criteria for AML), the combination treatment will be considered successful. If the true CR rate is 40%, then the trial will be considered successful with probability 0.06 (type I error). Conversely, if the true CR rate is 70%, then the trial will be considered successful with probability 0.89 (power).
Measured: up to 43 days (+/- 2 days)

Secondary outcomes (9)

Overall response rate (ORR)
{Percentage of patients?} with complete remission (CR), complete remission with incomplete count recovery (CRi), morphologic leukemia free state rate (MLFS), and partial response rate (PR) per AML Response Criteria.
Measured: 28 days (+/- 7 days) days post remission marrow collection
Progression-free survival (PFS)
PFS defined as the time between first dose of study treatment to the event of disease progression or death; analyzed using Kaplan Meier methods.
Measured: 6 months and 1 year following the conclusion of study enrollment
Overall survival (OS)
OS defined as the time from start of treatment to death; analyzed using Kaplan Meier methods.
Measured: 6 months and 1 year following the conclusion of study enrollment
Event free survival (EFS)
EFS defined as the time from start of treatment to resistant leukemia, relapsed leukemia, second malignancy, or death; analyzed using Kaplan Meier methods.
Measured: 6 months and 1 year following the conclusion of study enrollment
Mortality rate
Defined as whether the patient was alive 30 days post-study treatment start (died/not died).
Measured: 30 days post study treatment start
Allogeneic transplantation
Defined as the total number of patients requiring allogeneic transplantation after protocol treatment.
Measured: 1 year after study entry
Percentage of patients who develop drug-related non-hematologic grade 3 or higher toxicity
Percent of patients who develop drug-related non-hematologic grade 3 or higher toxicities within 30 days after study treatment initiation (excluding nausea and vomiting or electrolyte abnormalities that are corrected with standard clinical care).
Measured: 30 days post study treatment start
Number of patients who develop drug-related non-hematologic grade 3 or higher toxicity
Number of patients who develop drug-related non-hematologic grade 3 or higher toxicities within 30 days after study treatment initiation (excluding nausea and vomiting or electrolyte abnormalities that are corrected with standard clinical care).
Measured: 30 days post study treatment start
Bone marrow aplasia
Defined as a bone marrow biopsy with an overall cellularity of < 5% with no evidence of leukemia as well as an ANC <0.5 and a platelet count of < 10 requiring transfusion support.
Measured: up to 43 days (+/- 2 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Jun 202416 Aug 2025

First posted23 Mar 2023
Study start3 Jun 2024
Primary completion16 Aug 2025
Study completion16 Aug 2025

Why it stopped: Interim Analysis per Protocol

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Secondary Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe 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: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05780879
Sponsor's protocol ID: UMCC 2021.145
Other IDs: HUM00227799
Status last verified: May 2026
First submitted: 10 Mar 2023
Last updated: 24 Aug 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Secondary Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Proof of Concept Pilot Study of the Addition of Venetoclax to Standard Remission Induction Chemotherapy Fludarabine or Cladrabine, Cytarabine, and Granulocyte Colony Stimulating Factor (G-CSF) (FLAG or CLAG) for Frontline Therapy of Secondary Acute Myeloid Leukemia
ClinicalTrials.gov ID: NCT05780879
Acronym / sponsor ID: UMCC 2021.145
Conditions: Secondary Acute Myeloid Leukemia
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Interim Analysis per Protocol
Enrolment: 10 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Collaborators: Genentech, Inc.
Study start: 3 Jun 2024 (actual)
Primary completion: 16 Aug 2025 (actual)
Study completion: 16 Aug 2025 (actual)
First posted: 23 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.

The primary purpose of this study is to determine complete remission rate of a novel combination induction chemotherapy treatment based upon 20 patients with newly diagnosed secondary AML.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Venetoclax + FLAG or CLAG induction chemotherapy	Experimental	Drug: Venetoclax, Drug: FLAG or CLAG ProtocolInduction chemotherapy with FLAG starting on day 1 and venetoclax given on days 3-16. The G-CSF component of FLAG will continue until count recovery (ANC at least > 1000). FLAG dosing will be standard and uniform for all patients and venetoclax dosing will be determined according to institutional guidelines based on the prophylactic antifungal therapy chosen for use during induction therapy. Given the national shortage of Fludarabine, Cladrabine (5mg/m2/day IV over 2 hours) has been substituted (CLAG) with similar toxicity profile.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Patients have an established, pathologically confirmed diagnosis of newly diagnosed secondary acute myeloid leukemia (sAML) as defined by the 2016 World Health Organization criteria. Secondary AML includes:
Patients must not have received prior treatment for the diagnosis of secondary acute myeloid leukemia, with the exception of hydroxyurea and/or leukopheresis which are permitted until day 1 of study participation. Prior treatment for a diagnosis of MDS, MPN, or MDS/MPN overlap syndrome is allowed.
Patients ≥ 18 years of age.
ECOG PS ≤ 2
Patient has ability to understand and the willingness to sign a written informed consent.

Key exclusion criteria (32 listed)

Diagnosed with acute promyelocytic leukemia (acute leukemia with recurrent genetic abnormalities - APL with t(15;17)(q22;q12);PML-RARA).
Diagnosed with myeloid blast phase of chronic myeloid leukemia.
Diagnosed with isolated extramedullary AML
Diagnosed with acute leukemia of ambiguous lineage, acute biphenotypic or acute bilineal acute leukemia per the 2016 World Health Organization classification system.
Patients with a white blood cell count (WBC) >50,000 at the time of initiation of therapy will be excluded. Patients can consent and screen with a WBC > 50,000 but will require cytoreduction (hydrea or leukopheresis) prior to day 1 of therapy.

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
VenetoclaxVenetoclax administered orally once daily on days 3-16.	Drug	Venetoclax + FLAG or CLAG induction chemotherapy
FLAG or CLAG ProtocolFLAG consists of daily infusions of Fludarabine (30mg/m2/day over 30 minutes) and Ara-C (2g/m2/day over 4 hours) for 5 days with daily subcutaneous injections of G-CSF until count recovery. Tbo-filgrastim will be administered as follows: WBC count >50,000 - 5mcg/kg; WBC count <50,000 - hold Tbo-filgrastim. Given the national shortage of Fludarabine, Cladrabine (5mg/m2/day IV over 2 hours) has been substituted (CLAG) with similar toxicity profile.	Drug	Venetoclax + FLAG or CLAG induction chemotherapy

Primary outcome

Morphologic complete remission (CR)
Time frame: up to 43 days (+/- 2 days)
If at least 12/20 (60%) of patients achieve a CR (based upon a bone marrow aspiration, biopsy, and peripheral blood studies according to the International Working Group criteria for AML), the combination treatment will be considered successful. If the true CR rate is 40%, then the trial will be considered successful with probability 0.06 (type I error). Conversely, if the true CR rate is 70%, then the trial will be considered successful with probability 0.89 (power).

9 secondary outcomes

Overall response rate (ORR)
Time frame: 28 days (+/- 7 days) days post remission marrow collection
Progression-free survival (PFS)
Time frame: 6 months and 1 year following the conclusion of study enrollment
Overall survival (OS)
Time frame: 6 months and 1 year following the conclusion of study enrollment
Event free survival (EFS)
Time frame: 6 months and 1 year following the conclusion of study enrollment
Mortality rate
Time frame: 30 days post study treatment start
Allogeneic transplantation
Time frame: 1 year after study entry
Percentage of patients who develop drug-related non-hematologic grade 3 or higher toxicity
Time frame: 30 days post study treatment start
Number of patients who develop drug-related non-hematologic grade 3 or higher toxicity
Time frame: 30 days post study treatment start
Bone marrow aplasia
Time frame: up to 43 days (+/- 2 days)

Results and safety

The study was stopped early (reason given: Interim Analysis per Protocol). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
Individual participant dataSharing planned: No

Related trials for Secondary Acute Myeloid Leukemia

Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT
High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation
RecruitingPhase 2
Personalized NK Cell Therapy in CBT
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia
RecruitingObservational study
Cancer Experience Registry (CER) for Cancer Patients and Caregivers
Neoplasms, Cancer
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
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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.

Dale Bixby, MD, PhD principal investigator

University of Michigan Rogel Cancer Center

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 Venetoclax and FLAG or CLAG Protocol in people with Secondary Acute Myeloid Leukemia, run by University of Michigan Rogel Cancer Center 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 14 inclusion and 32 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: stopped early, as of the sponsor's last update on 24 Aug 2026. 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 stopped early (reason given: Interim Analysis per Protocol). Results are not available in the source record.

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?

Morphologic complete remission (CR) (time frame: up to 43 days (+/- 2 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05780879.

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 24 Aug 2026.