- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02115295
Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With AML, HR MDS, or Myeloid Blast Phase of CML
Study Overview
Status
Conditions
- Acute Myeloid Leukemia
- Previously Treated Myelodysplastic Syndrome
- Secondary Acute Myeloid Leukemia
- Untreated Adult Acute Myeloid Leukemia
- Myelodysplastic Syndrome
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Myeloid Leukemia
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- de Novo Myelodysplastic Syndrome
- Acute Biphenotypic Leukemia
- Blasts 10 Percent or More of Bone Marrow Nucleated Cells
- Blasts 10 Percent or More of Peripheral Blood White Cells
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Tapan Kadia
- Phone Number: 713-792-7305
- Email: tkadia@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Tapan M. Kadia
- Phone Number: 713-792-7305
-
Principal Investigator:
- Tapan M. Kadia
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
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 (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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (cladribine, cytarabine, idarubicin)
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. |
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete response (CR) rate
Time Frame: Up to 12 months
|
CR rate will be determined.
|
Up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: Up to 12 months
|
ORR will be determined.
|
Up to 12 months
|
Overall survival (OS)
Time Frame: Up to 12 months
|
OS will be assessed.
|
Up to 12 months
|
Event-free survival (EFS)
Time Frame: Up to 12 months
|
EFS will be assessed.
|
Up to 12 months
|
Duration of response
Time Frame: Up to 12 months
|
Duration of response will be assessed.
|
Up to 12 months
|
Incidence of toxicities
Time Frame: Up to 12 months
|
Safety and tolerability of cladribine in combination with idarubicin and cytarabine will be determined.
|
Up to 12 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Use of intrathecal prophylaxis
Time Frame: Up to 12 months
|
The relationship between patient/disease characteristics and use of intrathecal prophylaxis will be studied and described.
|
Up to 12 months
|
Incidence of leptomeningeal disease
Time Frame: Up to 12 months
|
The relationship between patient/disease characteristics and incidence of leptomeningeal disease will be studied and described.
|
Up to 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Tapan M Kadia, M.D. Anderson Cancer Center
Publications and helpful links
General Publications
- 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.
- 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.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Neoplastic Processes
- Precancerous Conditions
- Leukemia, Lymphoid
- Cell Transformation, Neoplastic
- Carcinogenesis
- Chronic Disease
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Preleukemia
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Leukemia, Biphenotypic, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Tyrosine Kinase Inhibitors
- Venetoclax
- Cytarabine
- Idarubicin
- Cladribine
- Midostaurin
- 2-chloro-3'-deoxyadenosine
- Staurosporine
- Gilteritinib
Other Study ID Numbers
- 2012-0648 (Other Identifier: M D Anderson Cancer Center)
- NCI-2014-01103 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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