Comparing the Addition of an Anti-Cancer Drug, Pomalidomide, to the Usual Chemotherapy Treatment (Daunorubicin and Cytarabine Liposome) in Newly Diagnosed Acute Myeloid Leukemia With Myelodysplastic Syndrome-Related Changes

Randomized Phase 2 Study of Daunorubicin and Cytarabine Liposome + Pomalidomide Versus Daunorubicin and Cytarabine Liposome in Newly Diagnosed AML With MDS-Related Changes

This phase II trial studies the effect of adding pomalidomide to usual chemotherapy treatment (daunorubicin and cytarabine liposome) in treating patients with newly diagnosed acute leukemia with myelodysplastic syndrome-related changes. Pomalidomide may stop the growth of blood vessels, stimulate the immune system, and kill cancer cells. Chemotherapy drugs, such as daunorubicin and cytarabine liposome, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding pomalidomide to chemotherapy treatment with daunorubicin and cytarabine liposome may be effective in improving some treatment outcomes in patients with newly diagnosed acute leukemia with myelodysplastic syndrome-related changes.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia Post Cytotoxic Therapy
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Drug: Pomalidomide; Procedure: Bone Marrow Aspiration and Biopsy

Detailed Description

PRIMARY OBJECTIVES:

I. To establish recommended phase 2 dose (RP2D) of pomalidomide after liposome-encapsulated daunorubicin-cytarabine (daunorubicin and cytarabine liposome) induction.

II. To compare the rate of overall complete response (CR)/complete response with incomplete hematologic recovery (CRi) with daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed acute myeloid leukemia (AML) with preexisting myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myeloproliferative neoplasm (MPN); therapy-related AML (t-AML); or AML with myelodysplasia-related changes (MRC) based on cytogenetics or morphologic dysplasia.

SECONDARY OBJECTIVES:

I. To evaluate and compare rates of CR (full hematologic recovery) between daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML or AML with MRC.

II. To evaluate and compare toxicities (including treatment-related mortality) of daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

III. To detect and compare the presence of minimal residual disease (MRD) by flow cytometry in those who achieve CR/CRi with daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

IV. To compare median event-free survival (EFS) of daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

V. To compare median overall survival (OS) of daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

VI. To compare median and 2-year disease-free survival (DFS) after CR/CRi with daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

VII. To compare rates of allogeneic stem cell transplant (SCT) after daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

EXPLORATORY OBJECTIVES:

I. To assess for molecular biomarkers, Aiolos expression, and immune correlates of response with daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

II. To assess for differences in MRD by molecular based platforms in daunorubicin and cytarabine liposome + pomalidomide versus daunorubicin and cytarabine liposome alone in newly diagnosed AML with preexisting MDS, CMML or MPN, t-AML, or AML with MRC based on cytogenetics or morphologic dysplasia.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 and then pomalidomide orally (PO) once daily (QD) beginning between days 21-30 for 14 days in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.

ARM B:

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.

After completion of study treatment, patients are followed up for 30 days, then up to 5 years after the start of induction therapy or until death, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • New York
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathological confirmation of AML as defined by histologic, morphologic, or cytological evidence/confirmation of >= 20% blasts in bone marrow aspirate and/or biopsy

• Must meet criteria for t-AML or AML with MRC as defined by the 5th Edition of the World Health Organization (WHO) Classification of Myeloid Neoplasms or the International Consensus Classification (ICC) of Myeloid Neoplasms. Patients must meet one of the following criteria:

  • Therapy-related AML (AML derived from prior chemotherapy or radiation therapy)
  • AML originating from prior hematologic malignancy (MDS, CMML, or MPN)

  • AML with myelodysplasia-related cytogenetic abnormalities:

    • One of the following cytogenetic abnormalities:

      • Complex karyotype (3 or more unrelated chromosomal abnormalities in the absence of other class-defining recurrent genetic abnormalities as defined by WHO or ICC)
      • -7/del(7q)
      • Del(5q)/t(5q)/add(5q)
      • +8
      • i(17q)
      • -17/add(17p) or del(17p)
      • Del(20q)
      • -13/del(13q)
      • Del(11q)
      • Del(12p)/t(12p)/add(12p)
      • idicX(q13)

  • AML with myelodysplasia-related mutations: Must have a mutation in one of the following genes:

    • ASXL1
    • BCOR
    • EZH2
    • RUNX1
    • SF3B1
    • SRSF2
    • STAG2
    • U2AF1
    • ZRSR2
• No prior treatment for AML other than cytoreductive doses of hydroxyurea or leukapheresis
• Age >= 18 and =< 75 years on day of signing informed consent are eligible who are planned for intensive chemotherapy. Because no dosing or adverse event data are currently available on the use of pomalidomide in combination with daunorubicin and cytarabine liposome in patients < 18 years of age, children are excluded from this study. Patients > 75 years are not candidates for intensive chemotherapy with daunorubicin and cytarabine liposome
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >= 60%)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) unless due to leukemic infiltration, Gilbert's Syndrome, or hemolysis
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN
• Creatinine >= 30 ml/min creatinine clearance by Cockcroft-gault
• Left ventricular ejection fraction (LVEF) >= 50%
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured with undetectable HCV viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Females of childbearing potential (FCBP), defined as a female who: 1) has reached menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) must have a negative pregnancy test 72 hours prior to the start of study therapy. For FCBPs in Arm A, they must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

• Patients with Wilson's Disease or Copper-related metabolic disorders
• Absolute blast count > 30 x 10^9/L (cytoreduction with leukapheresis or hydroxyurea can be used to achieve absolute blast count < 30 x 10^9/L prior to day 1 of treatment)
• Cumulative daunorubicin lifetime exposure > 330 mg/m^2 and > 180 mg/m^2 with prior mediastinal radiation therapy
• Patients with known active central nervous system leukemia should be excluded from this clinical trial because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients receiving intrathecal chemotherapy prophylaxis should receive pomalidomide >= 3 days after administration
• Patients with uncontrolled intercurrent illness including, but not limited to, active and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, and cardiac arrhythmia. Patients with infection under active treatment and controlled with antibiotics are eligible
• Known additional malignancy (with the exception of prior hematologic malignancies that have transformed to AML) that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical cancer or patients receiving maintenance treatments without active disease (for example, hormonal therapy for breast cancer or prostate cancer or other adjuvant chemotherapy approaches). Anti-cancer therapy as above should be discontinued > 72 hours prior to day 1 of treatment
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Receipt of prior allogeneic stem cell transplant
• Administration of any therapy for MDS, CMML, or MPN (conventional or unconventional) must be completed by 2 weeks prior to treatment with daunorubicin and cytarabine liposome. Use of strong CYP1A2 inhibitors should be avoided
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide (e.g. lenalidomide, thalidomide) or daunorubicin and cytarabine liposome or their excipients
• Development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, or similar drugs in the past
• Pregnant women are excluded from this study because pomalidomide is an immunomodulatory agent 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 pomalidomide, breastfeeding should be discontinued if the mother is treated with pomalidomide. These potential risks may also apply to other agents used in this study. Women of childbearing potential must be willing to undergo pregnancy testing
• Any other medical condition that in the opinion of investigator would place patient at increased risk for toxicity during pomalidomide treatment (i.e. history of recurrent or serious thromboembolic events such as massive pulmonary embolism)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm B (daunorubicin and cytarabine liposome); INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; Cytarabine-Daunorubicin Liposome for Injection; Daunorubicin and Cytarabine (Liposomal); Liposomal AraC-Daunorubicin CPX-351; Liposomal Cytarabine-Daunorubicin; Liposome-encapsulated Combination of Daunorubicin and Cytarabine; Vyxeos; Cytarabine and Daunorubicin Liposomal; CPX 351; CPX351; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspirate and biopsy
Experimental: Arm A (daunorubicin and cytarabine liposome, pomalidomide); INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 and then pomalidomide PO QD beginning between days 21-30 for 14 days in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.	Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351; Cytarabine-Daunorubicin Liposome for Injection; Daunorubicin and Cytarabine (Liposomal); Liposomal AraC-Daunorubicin CPX-351; Liposomal Cytarabine-Daunorubicin; Liposome-encapsulated Combination of Daunorubicin and Cytarabine; Vyxeos; Cytarabine and Daunorubicin Liposomal; CPX 351; CPX351; Drug: Pomalidomide; Given PO; Other Names: Pomalyst; Imnovid; 4-Aminothalidomide; Actimid; CC-4047; CC4047; CC 4047; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspirate and biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Complete Response (CR)/Complete Response With Incomplete Hematologic Recovery (CRi)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR With Full Hematologic Recovery (Absolute Neutrophil Count > 1 x 10^9/L and Platelets > 100 x 10^9/L)	Will be assessed and compared with both arms A and B.	Up to 5 years
Incidence of Adverse Events	Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0 and compared descriptively between Arms A and B. Serious adverse events are denoted by "[SAE]".	Up to 30 days after last dose, up to 2 years
Complete Response (CR) Without Minimal Residual Disease (MRD)	Will assess CR without MRD by flow cytometry via Hematologics, Inc. compare descriptively between Arms A and B.	Up to 5 years
Event-free Survival	Will be compared between Arms A and B.	From day 1 of liposome-encapsulated daunorubicin-cytarabine until no response is achieved, relapse or death, will be assessed for up to 5 years
Disease-free Survival (DFS)	Will be compared between Arms A and B.	From CR/CRi until relapse or death, assessed at 2 years
Disease-free Survival	Will be compared between Arms A and B.	From CR/CRi until relapse or death, assessed up to 5 years
Overall Survival (OS)	Will be compared between Arms A and B.	From randomization until death or last follow-up, assessed up to 5 years
Rate of Allogeneic Stem Cell Transplantation	Will be compared between Arms A and B.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joshua F Zeidner, Ohio State University Comprehensive Cancer Center LAO

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Actual): November 21, 2024
• Study Completion (Estimated): April 25, 2026

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Myeloproliferative Disorders; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Investigative Techniques; Therapeutics; Dosage Forms; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Drug Administration Routes; Drug Therapy; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Diagnostic Techniques, Surgical; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Nucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Membranes, Artificial; Drug Carriers; Biomimetic Materials; Cytarabine; Daunorubicin; Injections; Biopsy; Specimen Handling; pomalidomide; CPX-351; Liposomes
• Other Study ID Numbers: NCI-2021-01961 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); UM1CA186712 (U.S. NIH Grant/Contract); 10434 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No