Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia

NCT02115295 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2012-0648NCI-2014-01103
• Study Type: interventional
• Target: 508
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well cladribine, idarubicin, cytarabine, and venetoclax work in patients with acute myeloid leukemia, high-risk myelodysplastic syndrome, or blastic phase chronic myeloid leukemia. Drugs used in chemotherapy, such as cladribine, idarubicin, cytarabine, and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Acute Biphenotypic Leukemia; Acute Myeloid Leukemia; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blasts 10 Percent or More of Bone Marrow Nucleated Cells; Blasts 10 Percent or More of Peripheral Blood White Cells; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rate

  CR rate will be determined.

  Up to 12 months

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 12 months

• Overall survival (OS)

  Up to 12 months

• Event-free survival (EFS)

  Up to 12 months

• Duration of response

  Up to 12 months

• Incidence of toxicities

  Up to 12 months

Other Outcomes (2)

• Use of intrathecal prophylaxis

  Up to 12 months

• Incidence of leptomeningeal disease

  Up to 12 months

Study Arms (1)

Treatment (cladribine, cytarabine, idarubicin)

EXPERIMENTAL

INDUCTION: Patients receive cladribine IV and cytarabine IV over 1-2 hours on days 1-5 and idarubicin IV over 30-60 minutes on days 1-3. Patients with untreated AML and MDS also receive venetoclax PO on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO BID on days 6-19 or gilteritinib PO QD on days 1-14. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive cladribine IV and cytarabine IV over 1-2 hours on days 1-3 and idarubicin IV over 30-60 minutes on days 1-2. Patients with untreated AML and MDS also receive venetoclax PO on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO BID on days 6-19 or gilteritinib PO QD. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cladribine; Drug: Cytarabine; Drug: Gilteritinib; Drug: Idarubicin; Other: Laboratory Biomarker Analysis; Drug: Midostaurin; Drug: Venetoclax

Interventions

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (cladribine, cytarabine, idarubicin)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (cladribine, cytarabine, idarubicin)

Gilteritinib DRUG

Given PO

Also known as: ASP-2215, ASP2215, Xospata

Treatment (cladribine, cytarabine, idarubicin)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Treatment (cladribine, cytarabine, idarubicin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cladribine, cytarabine, idarubicin)

Midostaurin DRUG

Given PO

Also known as: CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC-412, PKC412, Rydapt

Treatment (cladribine, cytarabine, idarubicin)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (cladribine, cytarabine, idarubicin)

Eligibility Criteria

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

You may qualify if:

• Patients with a diagnosis of AML, Acute Biphenotypic Leukemia, or high risk MDS (\>/= 10% blasts or IPSS \>/= intermediate-2) will be eligible. Patients with CML in Myeloid Blast Phase are also eligible.
• For Frontline cohort (1 or 4): No prior potentially-curative therapy for leukemia. Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, ATRA, or a total dose of cytarabine up to 2g (for emergency use for stabilization) is allowed. Patients deemed able to receive venetoclax (ie. insurance clearance) will be assigned to Frontline cohort 4. Patients with secondary AMLwho have been treated for their antecedent myeloid neoplasm will be enrolled into the separate Secondary AML cohort.
• For Salvage cohort: Patients with previously treated, relapsed or refractory AML, Acute Biphenotypic Leukemia, or CML in Myeloid Blast Phase are eligible.
• Age \</= 65 years.
• Adequate organ function as defined below:
• liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN - or \<5 x ULN if related to leukemic involvement)
• kidney function (creatinine \< 1.5 x ULN ).
• known cardiac ejection fraction of \> or = 45% within the past 6 months
• ECOG performance status of ≤ 2.
• A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
• Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.

You may not qualify if:

• Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
• Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient with documented hypersensitivity to any of the components of the chemotherapy program.
• Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (4)

• Goulart H, Jabbour E, Short NJ, Kadia TM, Pemmaraju N, Takahashi K, Ravandi F, Konopleva M, Jain N. A Phase I/II Trial of Ruxolitinib with Chemotherapy for Patients with Relapsed and/or Refractory Philadelphia-like Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2025 Nov;25(11):800-807. doi: 10.1016/j.clml.2025.05.013. Epub 2025 May 20.

  PMID: 40500616 DERIVED

• Goulart H, Kantarjian H, Borthakur G, Daver N, DiNardo CD, Jabbour E, Pemmaraju N, Alvarado Y, Atluri H, Yilmaz M, Haddad FG, Marx KR, Rausch C, Loghavi S, Jain N, Garcia-Manero G, Ravandi-Kashani F, Kadia TM. Cladribine, idarubicin, and cytarabine (CLIA) for patients with relapsed and/or refractory acute myeloid leukemia: A single-center, single-arm, phase 2 trial. Cancer. 2025 Apr 15;131(8):e35840. doi: 10.1002/cncr.35840.

  PMID: 40193193 DERIVED

• Kadia TM, Reville PK, Borthakur G, Yilmaz M, Kornblau S, Alvarado Y, Dinardo CD, Daver N, Jain N, Pemmaraju N, Short N, Wang SA, Tidwell RSS, Islam R, Konopleva M, Garcia-Manero G, Ravandi F, Kantarjian HM. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. Lancet Haematol. 2021 Aug;8(8):e552-e561. doi: 10.1016/S2352-3026(21)00192-7.

  PMID: 34329576 DERIVED

• Morita K, Kantarjian HM, Wang F, Yan Y, Bueso-Ramos C, Sasaki K, Issa GC, Wang S, Jorgensen J, Song X, Zhang J, Tippen S, Thornton R, Coyle M, Little L, Gumbs C, Pemmaraju N, Daver N, DiNardo CD, Konopleva M, Andreeff M, Ravandi F, Cortes JE, Kadia T, Jabbour E, Garcia-Manero G, Patel KP, Futreal PA, Takahashi K. Clearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia. J Clin Oncol. 2018 Jun 20;36(18):1788-1797. doi: 10.1200/JCO.2017.77.6757. Epub 2018 Apr 27.

  PMID: 29702001 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myeloid, Acute; Blast Crisis; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Cladribine; Cytarabine; gilteritinib; Idarubicin; midostaurin; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Tapan M Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tapan Kadia

CONTACT

713-792-7305; tkadia@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 14, 2014
• First Posted: April 16, 2014
• Study Start: May 19, 2014
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (1)