Trial Title:
Trial of Cladribine and Low-Dose Cytarabine (LoDAC) Alternating With Decitabine vs. Hypomethylating Agents (HMA) Plus Venetoclax as Frontline Therapy for AML or High-Grade MDS in Patients Unfit for Intensive Induction
NCT ID:
NCT05766514
Condition:
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Conditions: Official terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Cytarabine
Azacitidine
Decitabine
Venetoclax
Cladribine
Conditions: Keywords:
acute myeloid leukemia
myelodysplastic syndrome
AML
MDS
induction therapy
low-dose cytarabine
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:
Cladribine
Description:
Subjects will be given 5 mg/m2 cladribine intravenously on days 1-5 of cycle 1 and on
days 1-3 of cycles 2, 5, 6, 9, 10, 13, 14, 17 and 18.
Arm group label:
Arm A (investigational arm): cladribine, cytarabine, and decitabine
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Subjects will be given 20 mg cytarabine subcutaneously twice daily on days 1-10 of cycles
1, 2, 5, 6, 9, 10, 13, 14, 17 and 18.
Arm group label:
Arm A (investigational arm): cladribine, cytarabine, and decitabine
Intervention type:
Drug
Intervention name:
Decitabine
Description:
Subjects will be given 20 mg/m2 decitabine intravenously on days 1-5 of cycles 3, 4, 7,
8, 11, 12, 15 and 16
Arm group label:
Arm A (investigational arm): cladribine, cytarabine, and decitabine
Intervention type:
Drug
Intervention name:
azacitidine or decitabine
Description:
Subjects will be given either 20 mg/m2 decitabine intravenously on days 1-5 of each cycle
or 75 mg/m2 azacitidine intravenously or subcutaneously on days 1-7 of each cycle. The
treating physician will determine which drug each subject will receive.
Arm group label:
Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Subject will take 400 mg venetoclax orally once daily on days 1-21 of each cycle.
Arm group label:
Arm B (control arm): azacitidine with venetoclax or decitabine with venetoclax
Summary:
This phase II, open-label, randomized trial will compare the efficacy of the novel
regimen of cladribine/low-dose cytarabine alternating with decitabine to the current
standard of care regimen of hypomethylating agents (decitabine or azacitidine) plus
venetoclax in patients with acute myeloid leukemia (AML) or high-grade myelodysplastic
syndrome (MDS) who are either elderly or unfit for intensive induction. Subjects will be
randomized to be treated with either cladribine/low-dose cytarabine alternating with
decitabine (Arm A) or decitabine or azacitadine plus venetoclax (Arm B).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age > 60 years.
- Adults < 60 years are eligible if deemed unfit for intensive induction by their
treating physician (or choose to receive a non-intensive regimen due to
patient's preference)
- Diagnosis of treatment-naive AML (excluding acute promyelocytic leukemia treated
with hydroxyurea) or high grade MDS defined as >10% marrow blasts or R-IPSS of
intermediate 2 risk or higher with > 10% bone marrow blasts, and 1 or more of the
following:
- Circulating blasts in peripheral blood
- Rapidly declining blood counts over the past 8 weeks, as determined by treating
investigator
- Transfusion dependence
- Adverse cytogenetic changes or molecular mutations with high risk of rapid
progression to AML, as determined by treating investigator
- Significant B-symptoms attributed to MDS (weight loss, fatigue, unexplained
fever, night sweats)
- Evidence of clonal evolution with emergence of new cytogenetic changes or new
mutations compared to previous bone marrow biopsy.
- White blood cell count < 25 K/uL. Cytoreduction with hydroxyurea is allowed prior to
enrollment to obtain white blood cell count < 25 K/uL.
- Subjects of childbearing potential (SOCBP) must have a negative pregnancy test and
agree to use of an adequate method of contraception to avoid pregnancy throughout
the study and for at least 4 months after the last dose of study drug. Prior to
study enrollment, subjects of childbearing potential must be advised of the
importance of avoiding pregnancy during trial participation and the potential risk
factors for an unintentional pregnancy. Subjects with partners of child-bearing
potential must agree to use physician-approved contraceptive methods (e.g.,
abstinence, condoms, vasectomy) throughout the study and should avoid conceiving
children for 4 months following the last dose of study drug.
Exclusion Criteria:
- Participants with acute promyelocytic leukemia (APML, APL, AML-M3)
- Patient with active central nervous system leukemia
- Karnofsky performance status < 50 at screening
- Karnofsky performance status of 40-50 is allowed to proceed on study if the
patient had a performance status of 50-100 at screening and the decline to 40
is deemed definitely related to disease (AML/MDS).
- Patients with AML with molecular mutations with FDA approved targeted therapies in
the first line setting.
- This includes FLT3 ITD/TKD + AML, IDH1+ AML. (Note: IDH2+ AML has targeted
therapy approved in relapsed setting only; FDA approval for first line setting
is pending and will be excluded once approval is obtained).
- Subjects with familial AML/MDS syndromes and those with inherited DNA repair
syndromes like Fanconi Anemia
- Concurrent illness that in the opinion of the Investigator would pose an undue risk
to the subject participating in this clinical study.
- Severe kidney impairment CrCL < 10 mL/min (per Cockcroft Gault equation) or
dialysis-depended renal failure
- Class III-IV NYHA heart failure
- Child-Pugh class C liver cirrhosis
- Known seropositivity or active viral infection with human immunodeficiency virus
(HIV), hepatis B virus (HBV), or hepatitis C virus (HCV) unless fully treated and
negative by PCR. Patients who are seropositive because of HBV vaccine are eligible.
- Subjects with uncontrolled life-threatening infections
- Subjects with fever (temperature > 38.3 C) thought to be related to AML/MDS are
eligible
- History of allergic reaction to hypomethylating agents (decitabine, azacitidine),
venetoclax, cladribine, or cytarabine.
- Active solid tumor malignancy requiring treatment within previous 2 years.
- Patients with prior history of malignancy who completed treatment > 2 years
prior to baseline are eligible to enroll if there is currently no evidence of
disease and all toxicities of prior treatments are resolved.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are
compulsorily detained for treatment of either a psychiatric or physical illness.
- Known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Florida
Address:
City:
Gainesville
Zip:
32608
Country:
United States
Contact:
Last name:
Jamie Knapp
Phone:
352-294-8970
Email:
jamidy00@ufl.edu
Investigator:
Last name:
Paul Crispen, MD
Email:
Principal Investigator
Start date:
November 2024
Completion date:
December 2030
Lead sponsor:
Agency:
University of Florida
Agency class:
Other
Source:
University of Florida
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05766514
