Trial Title:
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)
NCT ID:
NCT05554419
Condition:
Acute Myeloid Leukemia
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Acute Myeloid Leukemia Arising From Previous Myeloproliferative Neoplasm
Acute Myeloid Leukemia Post Cytotoxic Therapy
Secondary Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Myeloproliferative Disorders
Cytarabine
Azacitidine
Venetoclax
Daunorubicin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Given IV or SC
Arm group label:
ARM D (azacitidine, venetoclax)
Other name:
5 AZC
Other name:
5-AC
Other name:
5-Azacitidine
Other name:
5-Azacytidine
Other name:
5-AZC
Other name:
Azacytidine
Other name:
Azacytidine, 5-
Other name:
Ladakamycin
Other name:
Mylosar
Other name:
U-18496
Other name:
Vidaza
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
ARM A (cytarabine)
Arm group label:
ARM B (cytarabine, venetoclax)
Arm group label:
ARM C (liposomal daunorubicin-cytarabine, venetoclax)
Arm group label:
ARM D (azacitidine, venetoclax)
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IV
Arm group label:
ARM A (cytarabine)
Arm group label:
ARM B (cytarabine, venetoclax)
Other name:
.beta.-Cytosine arabinoside
Other name:
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-.beta.-D-Arabinofuranosylcytosine
Other name:
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
Other name:
1-Beta-D-arabinofuranosylcytosine
Other name:
1.beta.-D-Arabinofuranosylcytosine
Other name:
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
Other name:
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Other name:
Alexan
Other name:
Ara-C
Other name:
ARA-cell
Other name:
Arabine
Other name:
Arabinofuranosylcytosine
Other name:
Arabinosylcytosine
Other name:
Aracytidine
Other name:
Aracytin
Other name:
Aracytine
Other name:
Beta-Cytosine Arabinoside
Other name:
CHX-3311
Other name:
Cytarabinum
Other name:
Cytarbel
Other name:
Cytosar
Other name:
Cytosine Arabinoside
Other name:
Cytosine-.beta.-arabinoside
Other name:
Cytosine-beta-arabinoside
Other name:
Erpalfa
Other name:
Starasid
Other name:
Tarabine PFS
Other name:
U 19920
Other name:
U-19920
Other name:
Udicil
Other name:
WR-28453
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
ARM A (cytarabine)
Arm group label:
ARM B (cytarabine, venetoclax)
Arm group label:
ARM C (liposomal daunorubicin-cytarabine, venetoclax)
Arm group label:
ARM D (azacitidine, venetoclax)
Other name:
EC
Intervention type:
Drug
Intervention name:
Liposome-encapsulated Daunorubicin-Cytarabine
Description:
Given IV
Arm group label:
ARM C (liposomal daunorubicin-cytarabine, venetoclax)
Other name:
CPX 351
Other name:
CPX-351
Other name:
CPX351
Other name:
Cytarabine and Daunorubicin Liposomal
Other name:
Cytarabine-Daunorubicin Liposome for Injection
Other name:
Daunorubicin and Cytarabine (Liposomal)
Other name:
Liposomal AraC-Daunorubicin CPX-351
Other name:
Liposomal Cytarabine-Daunorubicin
Other name:
Liposome-encapsulated Combination of Daunorubicin and Cytarabine
Other name:
Vyxeos
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
ARM A (cytarabine)
Arm group label:
ARM B (cytarabine, venetoclax)
Arm group label:
ARM C (liposomal daunorubicin-cytarabine, venetoclax)
Arm group label:
ARM D (azacitidine, venetoclax)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
ARM B (cytarabine, venetoclax)
Arm group label:
ARM C (liposomal daunorubicin-cytarabine, venetoclax)
Arm group label:
ARM D (azacitidine, venetoclax)
Other name:
ABT 199
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC 0199
Other name:
GDC-0199
Other name:
GDC0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Summary:
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.
Detailed description:
PRIMARY OBJECTIVES:
I. To improve the rate of measurable residual disease (MRD) negative complete remission
(CR) in patients with acute myeloid leukemia (AML) who have achieved a MRD positive CR
after induction chemotherapy received in a myeloMATCH young adult basket tier-1 protocol.
II. To determine the rate of achieving MRD negative CR after 2 cycles of post-remission
therapy with cytarabine vs. cytarabine + venetoclax or liposome-encapsulated
daunorubicin-cytarabine (daunorubicin and cytarabine liposome) + venetoclax azacitidine +
venetoclax in AML or myelodysplastic syndrome (MDS) who were MRD positive post induction
therapy.
SECONDARY OBJECTIVES:
I. To determine the disease-free survival, overall survival in this group of patients.
II. Assess the percentage of patients who receive allogeneic hematopoietic stem cell
transplantation (HCT).
III. Compare toxicities of each experimental arm with the control arm.
EXPLORATORY OBJECTIVES:
I. Evaluate MRD kinetics by following patients with detectable MRD through tier 2 and
beyond.
II. Evaluate longer term outcomes by treatment arm, genomics, MRD outcome, and other
features as patients receive additional myeloMATCH therapies to generate testable
hypotheses for more precise patient selection for these therapies aimed at improving
outcomes.
OUTLINE: Patients are randomized to 1 of 4 arms.
ARM A: Patients receive cytarabine intravenously (IV) on study. Patients undergo bone
marrow aspiration and biopsy on study. Patients may also undergo echocardiogram (ECHO)
and/or multigated acquisition scan (MUGA) as clinically indicated.
ARM B: Patients receive cytarabine IV and venetoclax orally (PO) on study. Patients
undergo bone marrow aspiration and biopsy on study. Patients may also undergo ECHO and/or
MUGA as clinically indicated.
ARM C: Patients receive liposome-encapsulated daunorubicin-cytarabine IV and venetoclax
PO on study. Patients undergo bone marrow aspiration and biopsy on study. Patients may
also undergo ECHO and/or MUGA as clinically indicated.
ARM D: Patients receive azacitidine IV or subcutaneously (SC) and venetoclax PO on study.
Patients undergo bone marrow aspiration and biopsy on study. Patients may also undergo
ECHO and/or MUGA as clinically indicated.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Patient must have been assigned to this protocol by myeloMATCH master screening and
reassessment protocol (MSRP)/MATCHBOX. Patients thereby assigned will have attained
complete remission (CR) or CR with partial hematologic recovery (CRh) (defined as CR
with [absolute neutrophil count (ANC)] >= 500/mcL and/or platelets > 50/mcL) with
detectable MRD at time of assignment. MRD is defined as > 0.1% flow cytometry on
bone marrow (BM) biopsy as assessed by MDNet. The definition of CR or CRh may be
made +/- 2 weeks from BM biopsy
- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC)
who have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
- Patient must have recovered (i.e.: resolved to < grade 2) from adverse events
related to prior anti-cancer therapy at the time of randomization with the exception
of alopecia
- Absolute neutrophil count (ANC) >= 500/mcL (obtained =< 7 days prior to protocol
randomization)
- Platelets >= 50,000/mcL (obtained =< 7 days prior to protocol randomization)
- Total bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained =< 7 days
prior to protocol randomization)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3.0 x institutional ULN (obtained =< 7 days prior to protocol
randomization)
- Creatinine =< 1.5 x institutional ULN OR >= 50 mL/min.1.73 m^2 (obtained =< 7 days
prior to protocol randomization)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of randomization 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. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- 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
- Patients must be able to swallow oral tablets and be free of gastrointestinal (GI)
absorption issues
Exclusion Criteria:
- 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
- Patients must not have FLT3 TKD or ITD mutation. Patients with this mutation, will
be excluded from this study because myeloMATCH plans separate studies in tier-2 for
those patients
- Patient must not be receiving any other investigational agents at the time of
randomization
- Patient must not have history of allergic reactions attributed to compounds of
similar chemical or biologic composition to cytarabine, azacitidine, venetoclax or
daunorubicin and cytarabine liposome
- Patients must not have uncontrolled intercurrent illness including but not limited
to, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, or serious chronic gastrointestinal conditions associated with
diarrhea
Gender:
All
Minimum age:
18 Years
Maximum age:
59 Years
Healthy volunteers:
No
Start date:
August 16, 2024
Completion date:
January 31, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05554419
