Back to resultsCladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
Primary Purpose
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cladribine
Cytarabine
Gilteritinib
Idarubicin
Laboratory Biomarker Analysis
Midostaurin
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Acute Biphenotypic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Patients with a diagnosis of AML, acute biphenotypic leukemia, or high risk MDS (>= 10% blasts or International Prognostic Scoring System [IPSS] >= intermediate-2) will be eligible; patients with CML in myeloid blast phase are also eligible
- For frontline cohorts (1 or 4): no prior potentially curative therapy for leukemia; prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, tretinoin (ATRA), or a total dose of cytarabine up to 2 g (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 AML who 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
- Bilirubin =< 2 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if related to leukemic involvement
- Creatinine =<1.5 x ULN
- Known cardiac ejection fraction of >= 45% within the past 6 months
- Eastern Cooperative Oncology Group (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 or his legally authorized representative is required prior to their enrollment on the protocol
Exclusion Criteria:
- 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 (New York Heart Association [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
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (cladribine, cytarabine, idarubicin)
Arm Description
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.
Outcomes
Primary Outcome Measures
Complete response (CR) rate
CR rate will be determined.
Secondary Outcome Measures
Overall response rate (ORR)
ORR will be determined.
Overall survival (OS)
OS will be assessed.
Event-free survival (EFS)
EFS will be assessed.
Duration of response
Duration of response will be assessed.
Incidence of toxicities
Safety and tolerability of cladribine in combination with idarubicin and cytarabine will be determined.
Full Information
NCT ID
NCT02115295
First Posted
April 14, 2014
Last Updated
October 23, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02115295
Brief Title
Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
Official Title
Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With AML, HR MDS, or Myeloid Blast Phase of CML
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2014 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
458 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (cladribine, cytarabine, idarubicin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cladribine
Other Intervention Name(s)
2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gilteritinib
Other Intervention Name(s)
ASP-2215, ASP2215, Xospata
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Idarubicin
Other Intervention Name(s)
4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Midostaurin
Other Intervention Name(s)
CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC-412, PKC412, Rydapt
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Complete response (CR) rate
Description
CR rate will be determined.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
ORR will be determined.
Time Frame
Up to 12 months
Title
Overall survival (OS)
Description
OS will be assessed.
Time Frame
Up to 12 months
Title
Event-free survival (EFS)
Description
EFS will be assessed.
Time Frame
Up to 12 months
Title
Duration of response
Description
Duration of response will be assessed.
Time Frame
Up to 12 months
Title
Incidence of toxicities
Description
Safety and tolerability of cladribine in combination with idarubicin and cytarabine will be determined.
Time Frame
Up to 12 months
Other Pre-specified Outcome Measures:
Title
Use of intrathecal prophylaxis
Description
The relationship between patient/disease characteristics and use of intrathecal prophylaxis will be studied and described.
Time Frame
Up to 12 months
Title
Incidence of leptomeningeal disease
Description
The relationship between patient/disease characteristics and incidence of leptomeningeal disease will be studied and described.
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with a diagnosis of AML, acute biphenotypic leukemia, or high risk MDS (>= 10% blasts or International Prognostic Scoring System [IPSS] >= intermediate-2) will be eligible; patients with CML in myeloid blast phase are also eligible
For frontline cohorts (1 or 4): no prior potentially curative therapy for leukemia; prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, decitabine, tretinoin (ATRA), or a total dose of cytarabine up to 2 g (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 AML who 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
Bilirubin =< 2 mg/dL
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if related to leukemic involvement
Creatinine =<1.5 x ULN
Known cardiac ejection fraction of >= 45% within the past 6 months
Eastern Cooperative Oncology Group (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 or his legally authorized representative is required prior to their enrollment on the protocol
Exclusion Criteria:
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 (New York Heart Association [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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tapan Kadia
Phone
713-792-7305
Email
tkadia@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tapan M Kadia
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tapan M. Kadia
Phone
713-792-7305
First Name & Middle Initial & Last Name & Degree
Tapan M. Kadia
12. IPD Sharing Statement
Citations:
PubMed Identifier
34329576
Citation
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.
Results Reference
derived
PubMed Identifier
29702001
Citation
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.
Results Reference
derived
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website
Learn more about this trial
Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
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