Status:
RECRUITING
A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
Lead Sponsor:
M.D. Anderson Cancer Center
Conditions:
Myelodysplastic Syndromes
Myeloproliferative Chronic Myelomonocytic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomon...
Detailed Description
Primary Objectives: * To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk MDS with excess blasts and higher-risk CMML. * MDS ...
Eligibility Criteria
Inclusion
- Age \>/= 18 years.
- Diagnosis of MDS or CMML by WHO and:
- MDS relapsed cohort (Cohort A): MDS with IPSS-R score \>3.5 and \>5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- CMML relapsed cohort (Cohort B): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS HMA-naïve cohort (Cohort C): MDS with IPSS-R score \>3.5 and \>/= 10% blasts
- CMML HMA-naïve cohort (Cohort D): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of \>5cm below costal margin or by sonographic volumetric assessment, platelets \<100x109/L, Hgb level \<10g/dL, WBC \>13x109/L, clonal cytogenetic abnormality (other than monosomy Y) or high risk mutations (ASXL1, RUNX1, SETBP1, BRAF, NRAS, KRAS, PTPN11, NF1, CBL).
- MDS/MPN relapsed cohort (Cohort E): MDS/MPN-NOS, MDS/MPN with neutrophilia (atypical CML) or MDS/MPN-RS-T with \>5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS/MPN HMA-naïve cohort (Cohort F): MDS/MPN-NOS or MDS/MPN with neutrophilia (atypical CML) with
- \>/=10% blasts or
- with \>5% blasts at least one of the following high-risk features: splenomegaly \>5cm below costal margin, WBC \>13x109/L, high risk cytogenetic or molecular features (ASXL1, SETBP1, i(17q), TP53) or
- who might not be deemed to benefit from HMA therapy due to proliferative or extramedullary disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2
- Creatinine clearance \> 30 ml/min no end/stage renal disease (using Cockcroft-Gault)
- Adequate hepatic function with total bilirubin 2x ULN, AST or ALT 2.5 xULN unless deemed to be due to underlying disease involvement.
- Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
- Patient must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
- English and Non-English speaking patients will be allowed
Exclusion
- Uncontrolled infection not adequately responding to appropriate antibiotics
- New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<50% by echocardiogram or multigated acquisition (MUGA) scan.
- History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.
- Female patients who are pregnant or lactating.
- Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], double-barrier method \[spermidical jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study.
- Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
- Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
Key Trial Info
Start Date :
September 23 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2027
Estimated Enrollment :
60 Patients enrolled
Trial Details
Trial ID
NCT05365035
Start Date
September 23 2022
End Date
December 31 2027
Last Update
December 31 2025
Active Locations (1)
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1
M D Anderson Cancer Center
Houston, Texas, United States, 77030