Testing the Effects of Novel Therapeutics for Newly Diagnosed, Untreated Patients With High-Risk Acute Myeloid Leukemia (A MyeloMATCH Treatment Trial)
Purpose
This phase II MyeloMATCH treatment trial tests whether the standard approach of cytarabine and daunorubicin in comparison to the following experimental regimens works to shrink cancer in patients with high risk acute myeloid leukemia (AML): 1) daunorubicin and cytarabine liposome alone; 2) cytarabine and daunorubicin with venetoclax; 3) azacitidine and venetoclax; 4) daunorubicin and cytarabine liposome and venetoclax. "High-risk" refers to traits that have been known to make the AML harder to treat. Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Daunorubicin is in a class of medications called anthracyclines. It also works by slowing or stopping the growth of cancer cells in the body. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. 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. There is evidence that these newer experimental treatment regimens may work better in getting rid of more AML compared to the standard approach of cytarabine and daunorubicin.
Conditions
- Acute Myeloid Leukemia
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
- Acute Myeloid Leukemia Post Cytotoxic Therapy
- Acute Myeloid Leukemia, Myelodysplasia-Related
Eligibility
- Eligible Ages
- Between 18 Years and 59 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- STEP 1 REGISTRATION:
- Participants must have been registered to Master Screening and Re-Assessment
Protocol, MYELOMATCH, prior to consenting to this study. Participants must have been
assigned to this clinical trial, via MATCHBox, prior to registration to this study.
- Note: Pre-enrollment/diagnosis labs must have already been performed under the
MYELOMATCH
- Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) per
World Health Organization (WHO) criteria
- Participants must have high-risk (adverse) AML per European LeukemiaNet (ELN) 2017
criteria
- Participants with therapy-related AML (t-AML), or with AML evolving from an
antecedent hematologic disorder (such as myeloproliferative neoplasm), or AML with
myelodysplasia-related changes (AML-MRC) are eligible
- Acute promyelocytic leukemia is excluded
- Participants with favorable or intermediate risk disease are excluded
- Participants with FLT3 mutations (ITD or TKD) are excluded
- Participants with t(9;22) translocation are excluded
- A single dose of intrathecal chemotherapy is allowed prior to study entry
- Prior anthracycline therapy is allowed but must not exceed a cumulative lifetime
dose of 200 mg/m^2 daunorubicin or equivalent. Prior hypomethylating agent (HMA)
exposure is allowed, as long as not for AML diagnosis
- Participants must not have received or be currently receiving any prior therapy for
acute myeloid leukemia. Hydroxyurea to control the white blood cells (WBC) is
allowed prior to registration and initiation of protocol-defined therapy. All trans
retinoic acid (ATRA) given until a diagnosis of acute promyelocytic leukemia is
ruled out is also allowed.
- Participants must not be receiving or planning to receive any other investigational
agents before completing protocol therapy
- Participants must be between 18 and 59 years of age
- Participants must have Zubrod performance status =< 3 as determined by a history and
physical (H&P) completed within 14 days prior to registration
- Participants must have a complete medical history and physical exam within 7 days
prior to registration
- Participants must be able to swallow and retain oral medications and have no known
gastrointestinal disorders likely to interfere with absorption of oral medications
- Participants with known human immunodeficiency virus (HIV)-infection must be on
effective anti-retroviral therapy at time of registration and have undetectable HIV
viral load within 6 months prior to registration
- Participants with evidence of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load within 28 days prior to registration and be on
suppressive therapy, if indicated
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants with active HCV infection who are currently on
treatment must have an undetectable HCV viral load within 28 days prior to
registration
- The following tests must be performed within 14 days prior to registration to
establish baseline values:
- Complete blood count (CBC)/differential/platelets
- Total bilirubin
- Lactate dehydrogenase (LDH)
- Albumin
- Glucose
- Fibrinogen
- Participants must have adequate kidney function as evidenced by creatinine clearance
>= 30mL/min (by Cockcroft Gault) within 28 days prior to registration
- Participants must have adequate liver function as evidenced by aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of
normal (ULN), and total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has
a history of Gilbert's disease) within 28 days prior to registration
- Total bilirubin =< 2.0 x ULN (or 5.0 x ULN if the participant has a history of
Gilbert's disease) within 28 days prior to registration
- Participants must have adequate cardiac function as determined by echocardiography
or MUGA scan with an ejection fraction >= 50% within 28 days prior to registration
- Participants with a prior or concurrent malignancy whose natural history (in the
opinion of the treating physician) does not have the potential to interfere with the
safety or efficacy assessment of the investigational regimen are eligible for this
trial. No concurrent therapies for such malignancy are allowed with the exception of
hormonal therapy
- Participants with known history of Wilson's disease or other known copper-metabolism
disorder are excluded
- Participants must not be pregnant or nursing. Women/men of reproductive potential
must have agreed to use 2 contraception methods. A woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months. In addition to routine contraceptive methods (e.g., hormonal
contraceptives [examples include birth control pills, vaginal rings, or patches]
associated with inhibition of ovulation for at least 1 month prior to taking study
drug), "effective contraception" also includes heterosexual celibacy and surgery
intended to prevent pregnancy (or with a side-effect of pregnancy prevention)
defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation.
However, if at any point a previously celibate participant chooses to become
heterosexually active during the time period for use of contraceptive measures
outlined in the protocol, he/she is responsible for beginning contraceptive
measures. A barrier method should be used during this study along with hormonal
contraceptives from initial study drug administration to 30 days after the last dose
of study drug as drug-drug interaction with venetoclax is unknown
- Participants must have agreed to have specimens submitted for translational medicine
(MRD) under the myeloMATCH MSRP and specimens must be submitted
- Participants must be informed of the investigational nature of this study and must
sign and give informed consent in accordance with institutional and federal
guidelines
- As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has
been entered in the system
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm I (cytarabine, daunorubicin) |
Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV on days 1-3 per standard approach of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1-2. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
|
Experimental Arm II (cytarabine, daunorubicin, venetoclax) |
Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax PO on days 1-11 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 2-6 and daunorubicin IV on days 2-3 with venetoclax PO on days 1-8. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
|
Experimental Arm III (azacitidine, venetoclax) |
Patients receive azacitidine SC or IV on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
|
Experimental Arm IV (daunorubicin and cytarabine liposome) |
Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
|
Experimental Arm V (daunorubicin and cytarabine liposome, venetoclax) |
Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 and venetoclax PO on days 1-14 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3 and venetoclax PO on days 1-7. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35233
Phoenix 5308655, Arizona 5551752 85054
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Bloomington 4885164, Illinois 4896861 61701
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Canton 4831990, Illinois 4896861 61520
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414-805-3666
San Juan 4568127, Puerto Rico 00927
San Juan 4568127, Puerto Rico 00936
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More Details
- NCT ID
- NCT05554406
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
PRIMARY OBJECTIVE: I. To compare measurable residual disease (MRD) negative complete remission (CR) rates between each of the experimental regimens and cytarabine + daunorubicin (7+3). SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities with each of the regimens. II. To estimate complete remission (CR) rates, complete remission with incomplete count recovery (CRi, with and without MRD) rates, event-free survival (EFS), time to relapse, relapse-free survival (RFS), and overall survival (OS) with each of the regimens. III. To describe and compare MRD negative CR rates by genomic subgroups within and across randomized arms. BAKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients are randomized to 1 of 5 arms. ARM I: Patients receive cytarabine intravenously (IV) continuously on days 1-7 and daunorubicin IV on days 1-3 per standard approach of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 1-5 and daunorubicin IV on days 1-2. Patients undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM II: Patients receive cytarabine IV continuously on days 2-8 and daunorubicin IV on days 2-4 with venetoclax orally (PO) on days 1-11 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of cytarabine IV continuously on days 2-6 and daunorubicin IV on days 2-3 with venetoclax PO on days 1-8. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM III: Patients receive azacitidine subcutaneously (SC) or IV on days 1-7 and venetoclax PO on days 1-28 of each cycle. Cycles repeat every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM IV: Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. ARM V: Patients receive daunorubicin and cytarabine liposome IV over 90 minutes on days 1, 3, and 5 and venetoclax PO on days 1-14 of each cycle. Cycles repeat every 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity. Patients may receive an additional cycle of daunorubicin and cytarabine liposome IV over 90 minutes on days 1 and 3 and venetoclax PO on days 1-7. Patients undergo ECHO or MUGA scan during screening. Patients also undergo a bone marrow aspiration and collection of blood throughout the trial. After completion of study treatment, patients follow up every month for first year, every 2 months for the second year, every 3 months for the third year and every 6 months to year 5.