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

NCT05365035 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-1116NCI-2022-03803
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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 myelomonocytic leukemia (CMML).

Conditions

Myelodysplastic Syndromes; Myeloproliferative Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• To establish the overall survival (OS).

  through study completion, an average of 1 year

Study Arms (1)

cladribine, cytarabine, venetoclax, and azacitidine

EXPERIMENTAL

Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18

Drug: Cladribine; Drug: Cytarabine; Drug: Venetoclax; Drug: Azacitidine

Interventions

Cladribine DRUG

Given by Vein (IV)

Also known as: Leustatin®, 2-CdA

cladribine, cytarabine, venetoclax, and azacitidine

Cytarabine DRUG

Given under the skin; subcutaneous injection (SQ)

Also known as: Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochloride

cladribine, cytarabine, venetoclax, and azacitidine

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

cladribine, cytarabine, venetoclax, and azacitidine

Azacitidine DRUG

Given by IV or subcutaneous injection (SQ)

Also known as: 5-azacytidine, 5-aza, Vidaza™, 5-AZC, AZA-CR, Ladakamycin

cladribine, cytarabine, venetoclax, and azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Cladribine; Cytarabine; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Aza Compounds; Organic Chemicals

Study Officials

• Guillermo Bravo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillermo Bravo, MD

CONTACT

(713) 794-3604; gmontalban1@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2022
• First Posted: May 6, 2022
• Study Start: September 23, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (1)