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Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With Acute Myeloid Leukemia (AML), High Risk Myelodysplastic Syndrome (HR MDS) or Myeloid Blast Phase of Chronic Myeloid Leukemia (CML)

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ClinicalTrials.gov Identifier: NCT02115295
Recruitment Status : Recruiting
First Posted : April 16, 2014
Last Update Posted : June 27, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if the combination of cladribine, idarubicin, and cytarabine can help to control AML, high risk MDS, and/or CML in blast phase. Midostaurin may also be added to the combination for patients with a specific type of AML and the affect on the disease will be studied. The safety of these drugs will also be studied.

This is an investigational study. Cladribine, cytarabine, and idarubicin are all FDA approved and commercially available for the treatment of different kinds of leukemia Midostaurin is FDA approved and commercially available to treat a specific type of AML in combination with chemotherapy. It is investigational to use these drugs in combination with each other. The study doctor can explain how the study drugs are designed to work.

Up to 308 patients will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Drug: Cladribine Drug: Cytarabine Drug: Idarubicin Behavioral: Phone Calls Drug: Midostaurin Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Cladribine Plus Idarubicin Plus Cytarabine (ARAC) in Patients With Acute Myeloid Leukemia (AML), High Risk Myelodysplastic Syndrome (HR MDS) or Myeloid Blast Phase of Chronic Myeloid Leukemia (CML)
Actual Study Start Date : May 2014
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019


Arm Intervention/treatment
Experimental: Frontline, Untreated AML/MDS

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5. Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5. Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3. Age < 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3. Idarubicin 8 mg/m2/day by vein on Days 1 - 2.

One cycle of therapy is considered 4 weeks. After last dose of study drug, participant called every 6 -12 months by a member of the study staff to ask about any side effects they may be having. The phone call should take about 5-10 minutes.

AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.

Drug: Cladribine

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3.

Other Names:
  • Leustatin
  • 2-CdA

Drug: Cytarabine

Induction Phase:

Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5

Consolidation Phase:

Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3.

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Drug: Idarubicin

Induction Phase:

Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Idarubicin 8 mg/m2/day by vein on Days 1 - 2.


Behavioral: Phone Calls
After last dose of study drug, participant called every 6 -12 months by a member of the study staff to ask about any side effects they may be having. The phone call should take about 5-10 minutes.

Drug: Midostaurin
AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.
Other Name: PKC412

Experimental: Relapsed or Refractory AML

Relapsed or refractory AML requiring salvage chemotherapy.

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5. Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5. Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3. Age < 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3. Idarubicin 8 mg/m2/day by vein on Days 1 - 2.

One cycle of therapy is considered 4 weeks. After last dose of study drug, participant called every 6 -12 months by a member of the study staff to ask about any side effects they may be having.

AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.

Drug: Cladribine

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3.

Other Names:
  • Leustatin
  • 2-CdA

Drug: Cytarabine

Induction Phase:

Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5

Consolidation Phase:

Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3.

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Drug: Idarubicin

Induction Phase:

Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Idarubicin 8 mg/m2/day by vein on Days 1 - 2.


Behavioral: Phone Calls
After last dose of study drug, participant called every 6 -12 months by a member of the study staff to ask about any side effects they may be having. The phone call should take about 5-10 minutes.

Drug: Midostaurin
AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.
Other Name: PKC412

Experimental: Secondary AML

Secondary AML who have received treatment for their antecedent myeloid disorder.

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5. Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5. Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3. Age < 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3. Idarubicin 8 mg/m2/day by vein on Days 1 - 2.

One cycle of therapy is considered 4 weeks. After last dose of study drug, participant called every 6 -12 months.

AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.

Drug: Cladribine

Induction Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 5.

Consolidation Phase:

Cladribine 5 mg/m2/day by vein on Days 1 - 3.

Other Names:
  • Leustatin
  • 2-CdA

Drug: Cytarabine

Induction Phase:

Age < 60 years: Cytarabine 2 grams/m2 by vein on Days 1 - 5. Age > or = 60 years: Cytarabine 1.5 grams/m2 by vein on Days 1 - 5

Consolidation Phase:

Cytarabine 1.5 grams/m2 by vein on Days 1 - 3. Age > or = 60 years: Cytarabine 1 grams/m2 by vein on Days 1 - 3.

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Drug: Idarubicin

Induction Phase:

Idarubicin 10 mg/m2/day by vein on Days 1 - 3.

Consolidation Phase:

Idarubicin 8 mg/m2/day by vein on Days 1 - 2.


Behavioral: Phone Calls
After last dose of study drug, participant called every 6 -12 months by a member of the study staff to ask about any side effects they may be having. The phone call should take about 5-10 minutes.

Drug: Midostaurin
AML patients with known FLT3-ITD or FLT3 kinase domain mutations allowed to receive Midostaurin at the recommended dose of 50 mg orally twice daily on days 6-20 during induction, and then on days 6-20 during consolidation.
Other Name: PKC412




Primary Outcome Measures :
  1. Complete Response Rate (CR) [ Time Frame: 21 days ]

    Patient's classified as achieving a complete response if they have complete remission (CR) or complete remission without platelet recovery (CRp). Patients who do not have evidence of a complete response considered not to have a complete response, regardless of the reason, including early withdrawals for any reason.

    Complete response rate (CR) defined as disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count ≥ 1.0 x 109/L and platelet count ≥ 100 x 109/L, and bone marrow differential showing ≤ 5% blasts. Response Criteria according to revised recommendations of the International Working Group Response Criteria (IWGRC) in acute myeloid leukemia.



Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 21 days ]

    Overall response defined as complete remission (CR), complete remission without platelet recovery (CRi), or partial remission (PR). Patients who do not have evidence of overall response considered to not have an overall response, regardless of the reason.

    Complete remission without platelet recovery (CRi) defined as participants meeting all criteria for CR, except for either residual neutropenia (ANC < 1.0 x 109/L) or thrombocytopenia (platelet count < 100 x 109/L).

    Partial remission (PR) defined as blood count recovery as for CR, but with a decrease in marrow blasts of at least 50% and not more than 6 to 25% abnormal cells in the bone marrow.

    Complete remission (CR) defined as disappearance of all clinical and/or radiologic evidence of disease, including extramedullary leukemia. Neutrophil count ≥ 1.0 x 109/L and platelet count ≥ 100 x 109/L, and bone marrow differential showing ≤ 5% blasts.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. For Frontline cohort: 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 with secondary AMLwho have been treated for their antecedent myeloid neoplasm will be enrolled into the separate Secondary AML cohort.
  3. For Salvage cohort: Patients with previously treated, relapsed or refractory AML, Acute Biphenotypic Leukemia, or CML in Myeloid Blast Phase are eligible.
  4. Age </= 65 years.
  5. 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
  6. ECOG performance status of </= 2.
  7. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
  8. 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:

  1. 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.
  2. 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.
  3. Patient with documented hypersensitivity to any of the components of the chemotherapy program.
  4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02115295


Contacts
Contact: Tapan Kadia, MD 713-792-7305

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Tapan Kadia, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02115295     History of Changes
Other Study ID Numbers: 2012-0648
NCI-2014-01103 ( Registry Identifier: NCI CTRP )
First Posted: April 16, 2014    Key Record Dates
Last Update Posted: June 27, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Idarubicin
Idamycin
Leukemia
Acute Myeloid Leukemia
AML
High Risk Myelodysplastic Syndrome
HR MDS
Myeloid Blast Phase of Chronic Myeloid Leukemia
CML
Acute Biphenotypic Leukemia
Cladribine
Leustatin
2-CdA
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride
Phone calls

Additional relevant MeSH terms:
Idarubicin
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myeloproliferative Disorders
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Pathologic Processes
Cytarabine
Cladribine
Midostaurin
Staurosporine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors