Acute Biphenotypic LeukemiaPhase 2NCT02115295
Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
A Phase 2 study testing Cladribine, Cytarabine and Gilteritinib in people with Acute Biphenotypic Leukemia and Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- What is being tested?
- Cladribine, Cytarabine and Gilteritinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 508 participants
- Where
- 1 siteUnited States
- Study dates
- 19 May 2014to 31 May 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Tapan M. Kadia, 713-792-7305
Tapan M. Kadia
About this study
Official title: Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With AML, HR MDS, or Myeloid Blast Phase of CML
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.
Read the detailed description
Primary Objectives:
- To determine the complete response rate (CR) of cladribine in combination with idarubicin and cytarabine (araC) in patients with acute myeloid leukemia (AML), high risk (HR) myelodysplastic syndrome (MDS), or myeloid blast phase of chronic myeloid leukemia (CML).
Secondary Objectives:
- To determine the overall response rate (ORR) of cladribine in combination with idarubicin and araC in patients with AML, HR MDS, or myeloid blast phase of CML.
II. To assess overall survival (OS) and event free survival (EFS) of patients treated with cladribine, idarubicin, and araC (cytarabine).
III. To assess the duration of response to the combination in patients with AML, HR MDS, or myeloid blast phase of CML.
IV. To determine the safety and tolerability of the combination in patients with AML, HR MDS, or myeloid blast phase of CML.
Exploratory Objectives:
- To study and describe the relationship between pretreatment patient/disease characteristics (including AML-associated molecular abnormalities) and outcome.
II. To identify molecular biomarkers predictive of response to therapy.
III. To study and describe the relationship between patient/disease characteristics, use of intrathecal prophylaxis, and incidence of leptomeningeal disease.
IV. To study the trajectories of leukemia mutations and molecular minimal residual disease (MRD) during the therapy.
OUTLINE:
INDUCTION: Patients receive cladribine intravenously (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 orally (PO) on days 2-8. AML patients with known FLT3-ITD or FLT3 kinase domain mutations may receive midostaurin PO twice daily (BID) on days 6-19 or gilteritinib PO once daily (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.
After completion of study treatment, patients are followed up every 6-12 months.
- 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
- Being tested
- Cladribine, Cytarabine, Gilteritinib, Idarubicin, Laboratory Biomarker Analysis
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute, Blast Crisis, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called 2-CdA, 2CDA, CdA, Cladribina
Given IV
CytarabineDrug
Also called .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
Given IV
GilteritinibDrug
Also called ASP-2215, ASP2215, Xospata
Given PO
IdarubicinDrug
Also called 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
MidostaurinDrug
Also called CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Gilteritinib; Drug: Idarubicin; Other: Laboratory Biomarker Analysis; Drug: Midostaurin; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR) rate
CR rate will be determined.
Measured: Up to 12 months
Secondary outcomes (5)
Overall response rate (ORR)
ORR will be determined.
Measured: Up to 12 months
Overall survival (OS)
OS will be assessed.
Measured: Up to 12 months
Event-free survival (EFS)
EFS will be assessed.
Measured: Up to 12 months
Duration of response
Duration of response will be assessed.
Measured: Up to 12 months
Incidence of toxicities
Safety and tolerability of cladribine in combination with idarubicin and cytarabine will be determined.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2014 (estimated)
- Study start19 May 2014
- Primary completion31 May 2030 (estimated)
- Study completion31 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute Biphenotypic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 508 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tapan M Kadia, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115295
- Sponsor's protocol ID
- 2012-0648
- Other IDs
- NCI-2014-01103, 2012-0648
- Status last verified
- May 2026
- First submitted
- 14 Apr 2014
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40500616Goulart 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.
PubMed 40193193Kadia 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.
PubMed 34329576Morita 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.
PubMed 29702001