Clinical Trials /

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

NCT02115295

Description:

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.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2012-0648
  • SECONDARY ID: NCI-2014-01103
  • SECONDARY ID: 2012-0648
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02115295

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

Interventions

DrugSynonymsArms
Cladribine2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251Treatment (cladribine, cytarabine, idarubicin)
Cytarabine.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-28453Treatment (cladribine, cytarabine, idarubicin)
GilteritinibASP-2215, ASP2215, XospataTreatment (cladribine, cytarabine, idarubicin)
Idarubicin4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDRTreatment (cladribine, cytarabine, idarubicin)
MidostaurinCGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC-412, PKC412, RydaptTreatment (cladribine, cytarabine, idarubicin)
VenetoclaxABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, VenclyxtoTreatment (cladribine, cytarabine, idarubicin)

Purpose

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.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cladribine, cytarabine, idarubicin)ExperimentalINDUCTION: 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.
  • Cladribine
  • Cytarabine
  • Gilteritinib
  • Idarubicin
  • Midostaurin
  • Venetoclax

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; 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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response (CR) rate
Time Frame:Up to 12 months
Safety Issue:
Description:CR rate will be determined.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 12 months
Safety Issue:
Description:ORR will be determined.
Measure:Overall survival (OS)
Time Frame:Up to 12 months
Safety Issue:
Description:OS will be assessed.
Measure:Event-free survival (EFS)
Time Frame:Up to 12 months
Safety Issue:
Description:EFS will be assessed.
Measure:Duration of response
Time Frame:Up to 12 months
Safety Issue:
Description:Duration of response will be assessed.
Measure:Incidence of toxicities
Time Frame:Up to 12 months
Safety Issue:
Description:Safety and tolerability of cladribine in combination with idarubicin and cytarabine will be determined.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 14, 2019