Testing the Use of Combination Therapy in Patients With Persistent Low Level Acute Myeloid Leukemia Following Initial Treatment, The ERASE Study (A MyeloMATCH Treatment Trial)
This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and venetoclax vs. azacitidine and venetoclax for treating patients who have residual disease after treatment for acute myeloid leukemia (AML). Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Liposome-encapsulated daunorubicin-cytarabine is a drug formulation that delivers daunorubicin and cytarabine in small spheres called liposomes, which may make the drugs safer or more effective. Azacitidine is a drug that interacts with DNA and leads to the activation of tumor suppressor genes, which are genes that help control cell growth. This study may help the study doctors find out if the different drug combinations are equally effective to the usual approach of cytarabine alone while requiring a shorter duration of treatment. To decide if they are better, the study doctors will be looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to cytarabine alone.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Patient must be >= 18 and =< 59 years of age
Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patient must have morphologically documented AML or secondary AML (from prior conditions such as myelodysplastic syndrome [MDS], myeloproliferative neoplasm [MPN]) or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria
Patient must have completed induction chemotherapy in a myeloMATCH young adult tier-1 protocol. Patient may have received prior hypomethylating agents (HMAs). Patient may have received prior azacitidine + venetoclax
Disqualifiers
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and continue for 6 months after the last dose of daunorubicin + cytarabine liposome, 6 months after the last dose of azacitidine for patients of childbearing potential, 3 months after the last dose of azacitidine for male patients, and for 30 days after the last dose of venetoclax. Patient must also abstain from nursing an infant for 2 weeks after the last dose of daunorubicin + cytarabine liposome and for 1 week after the last dose of azacitidine
Trial design
Design model
Parallel
Treatments tested in this trial
Azacitidine
Drug
Given IV or SC
Bone Marrow Aspiration and Biopsy
Procedure/Surgery
Undergo bone marrow aspiration and biopsy
Cytarabine
Drug
Given IV
Echocardiography Test
Procedure/Surgery
Undergo ECHO
Liposome-encapsulated Daunorubicin-Cytarabine
Drug
Given IV
Multigated Acquisition Scan
Procedure/Surgery
Undergo MUGA
Venetoclax
Drug
Given PO
Treatment groups
184 Participants
are divided into 4 treatment groups
Group A: ARM A (cytarabine)Active comparator 4 interventions
Group B: ARM B (cytarabine, venetoclax)Experimental treatment 5 interventions
Group C: ARM C (liposomal daunorubicin-cytarabine, venetoclax)Experimental treatment 5 interventions
Group D: ARM D (azacitidine, venetoclax)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Frequency of measurable residual disease (MRD) negative complete remission (CR)
Will be centrally evaluated. The MRD negative CR frequency will be compared between each experimental arm and the standard therapy arm using Fisher's exact test with one-sided alpha of 0.10 for each comparison. Test results with one-sided p-value \< 0.10 will be considered statistically significant. Multivariable logistic regression modeling will also be used to examine the treatment effect between each experimental arm and the standard therapy arm, adjusting for stratification factors and other possible clinical and biological risk factors.
Time frame
Following 2 cycles of consolidation (56 days)
Secondary outcomes
1
Overall survival
Estimates, including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparison between each experimental arm and the standard therapy arm will be conducted using the one-sided log-rank test. Only nominal p-values will be provided. Cox proportional hazards models will also be used to assess the treatment effect, adjusting for stratification factors and other possible clinical and biological risk factors.
Time frame
Between randomization and death from any cause, assessed up to 10 years
2
Disease-free survival
Estimates, including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparison between each experimental arm and the standard therapy arm will be conducted using the one-sided log-rank test. Only nominal p-values will be provided. Cox proportional hazards models will also be used to assess the treatment effect, adjusting for stratification factors and other possible clinical and biological risk factors.
Time frame
From randomization to relapse or death in remission, assessed up to 10 years
3
Rate of allogeneic transplant
Time frame
Up to 10 years
4
Incidence of adverse events
Toxicity will be determined using the Common Terminology Criteria for Adverse Events (CTCAE).
Time frame
Up to 10 years
Other outcomes
Locations
This trial has no locations.
Sponsors and contacts
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