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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Undergo collection of blood samples
Undergo bone marrow aspirate and biopsy
Given IV
Given PO
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, United States
...and 1 more locations
Rate of Complete Response (CR)/Complete Response With Incomplete Hematologic Recovery (CRi)
Time frame: Up to 2 years
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.
Time frame: 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 "\[SAE\]".
Time frame: 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.
Time frame: Up to 5 years
Event-free Survival
Will be compared between Arms A and B.
Time frame: 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.
Time frame: From CR/CRi until relapse or death, assessed at 2 years
Disease-free Survival
Will be compared between Arms A and B.
Time frame: From CR/CRi until relapse or death, assessed up to 5 years
Overall Survival (OS)
Will be compared between Arms A and B.
Time frame: 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.
Time frame: Up to 5 years
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