Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

May 3, 2017 updated by: Children's Oncology Group

A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination With Cytarabine in Pediatric Patients With Refractory/Relapsed Leukemia

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia. (Phase I closed to enrollment as of 09/16/09)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To define the overall response rate (complete remission or remission without platelet recovery) in young patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) treated with clofarabine in combination with cytarabine.

Secondary

  • To determine the safety profile and tolerability of clofarabine when given in combination with cytarabine in patients with and without prior stem cell transplantation.
  • To identify apoptosis specific genes that are important in mediating response to clofarabine and cytarabine.
  • To quantitate the level of human equilibrative nucleoside transporter proteins (hENT1 and hENT2) and human concentrative nucleoside transporter proteins (hCNT2 and hCNT3) in blasts of these patients.
  • To determine gene expression profiles at study entry and at time of relapse in order to isolate profiles that may predict response and also to complement apoptosis specific protein arrays.
  • To perform serial measurements of minimal residual disease (MRD) to provide an objective determination of the effectiveness of this treatment regimen and to correlate with post remission events (relapse, death).
  • To perform FLT3/ITD analysis to help determine the prevalence and clinical significance of this somatic mutation in patients with relapsed AML.

OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by a phase II study. Patients are stratified according to disease (acute lymphoblastic leukemia [ALL] vs acute myeloid leukemia [AML]). (Phase I closed to accrual as of 09/16/09)

  • Intrathecal CNS prophylaxis (all patients with ALL and at physician's discretion for patients with AML or acute leukemia of ambiguous lineage): Patients receive intrathecal (IT) cytarabine on day 0 of the first course of induction therapy. Patients also receive IT methotrexate on day 1 of the second course of induction therapy and on day 1 of all courses of maintenance therapy.

  • Induction therapy:

    • Course 1: Patients receive cytarabine IV over 2 hours and clofarabine IV over 2 hours on days 1-5. Patients with ≥ 5% blasts (i.e., M2 or M3 bone marrow) at days 14-21 proceed immediately to course 2 of induction therapy. Patients with < 5% blasts (i.e., M1 bone marrow) may proceed to course 2 of induction therapy at blood count recovery or at day 42.
    • Course 2: Patients receive clofarabine IV over 2 hours followed by cytarabine IV over 2 hours on days 1-5. After the second course of induction therapy, patients with M2 or M3 bone marrow at days 14-21 are removed from the study. Patients with M1 bone marrow proceed to maintenance therapy 14-42 days after the initiation of course 2.
  • Maintenance therapy: Patients receive clofarabine and cytarabine as in induction therapy. Treatment repeats every 14-42 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies.

After completion of study therapy, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3J 3G9
        • IWK Health Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hôpital Sainte Justine
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre at Pasqua Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • UAB Comprehensive Cancer Center
    • California
      • Downey, California, United States, 90027
        • Southern California Permanente Medical Group
      • Long Beach, California, United States, 90801
        • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
      • Madera, California, United States, 93638-8762
        • Children's Hospital Central California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Diego, California, United States, 92123-4282
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado Center for Cancer and Blood Disorders
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • District of Columbia
      • Washington, D.C., District of Columbia, United States, 20007
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
      • Washington, D.C., District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Lee Cancer Care of Lee Memorial Health System
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic - Orlando
      • Pensacola, Florida, United States, 32504
        • Nemours Children's Clinic - Pensacola
      • Tampa, Florida, United States, 33607
        • St. Joseph's Cancer Institute at St. Joseph's Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
      • Savannah, Georgia, United States, 31403-3089
        • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Cancer Research Center of Hawaii
    • Illinois
      • Chicago, Illinois, United States, 60612-7243
        • University of Illinois Cancer Center
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
      • Springfield, Illinois, United States, 62794-9677
        • Simmons Cooper Cancer Institute
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46260
        • St. Vincent Indianapolis Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40232
        • Kosair Children's Hospital
    • Louisiana
      • Alexandria, Louisiana, United States, 71315-3198
        • Tulane Cancer Center Office of Clinical Research
    • Maine
      • Bangor, Maine, United States, 04401
        • CancerCare of Maine at Eastern Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
      • Baltimore, Maryland, United States, 21215
        • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMASS Memorial Cancer Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0286
        • C.S. Mott Children's Hospital at University of Michigan Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Helen DeVos Children's Hospital at Spectrum Health
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Cancer Clinic
    • Missouri
      • Columbia, Missouri, United States, 65203
        • Ellis Fischel Cancer Center at University of Missouri - Columbia
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Nevada
      • Las Vegas, Nevada, United States, 89109-2306
        • CCOP - Nevada Cancer Research Foundation
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
      • Morristown, New Jersey, United States, 07962
        • Overlook Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
      • Newark, New Jersey, United States, 07112
        • Newark Beth Israel Medical Center
      • Paterson, New Jersey, United States, 07503
        • St. Joseph's Hospital and Medical Center
    • New York
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
      • Rochester, New York, United States, 14642
        • James P. Wilmot Cancer Center at University of Rochester Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Charlotte, North Carolina, United States, 28232-2861
        • Blumenthal Cancer Center at Carolinas Medical Center
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Cancer Center at Presbyterian Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Cleveland, Ohio, United States, 44106-5000
        • Rainbow Babies and Children's Hospital
      • Columbus, Ohio, United States, 43205-2696
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404-1815
        • Dayton Children's - Dayton
    • Oregon
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center and Children's Hospital
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Children's Hospital
      • Philadelphia, Pennsylvania, United States, 19104-9786
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh of UPMC
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Palmetto Health South Carolina Cancer Center
      • Greenville, South Carolina, United States, 29605
        • Greenville Hospital Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75390
        • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-2399
        • Baylor University Medical Center - Houston
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84113-1100
        • Primary Children's Medical Center
    • Virginia
      • Norfolk, Virginia, United States, 23507-1971
        • Children's Hospital of The King's Daughters
      • Roanoke, Virginia, United States, 24014
        • Carilion Medical Center for Children at Roanoke Community Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
      • Spokane, Washington, United States, 99220-2555
        • Providence Cancer Center at Sacred Heart Medical Center
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic - Marshfield Center
      • Milwaukee, Wisconsin, United States, 53226
        • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:

    • Acute myeloid leukemia (AML) with ≥ 5% blasts in the bone marrow (M2/M3 bone marrow) with or without extramedullary disease
    • Acute lymphoblastic leukemia (ALL) with > 25% blasts in the bone marrow (M3 bone marrow) with or without extramedullary disease
    • Acute leukemia of ambiguous lineage with ≥ 5% blasts in the bone marrow (M2/M3 bone marrow) with or without extramedullary disease

  • Disease must have relapsed after or be refractory to prior induction therapy

    • Patients with AML or acute leukemia of ambiguous lineage must be in first relapse OR refractory to first induction therapy with ≤ 1 attempt at remission induction

      • Patients with AML who enroll on the phase I portion of the study must have received prior mitoxantrone hydrochloride and cytarabine for newly diagnosed AML (phase I closed to accrual as of 09/16/09)

    • Patients with ALL must be in second or third relapse (≤ 3 prior induction regimens) OR refractory to reinduction in first relapse

      • Patients with ALL refractory to first induction therapy are not eligible
  • No acute promyelocytic leukemia
  • No CNS 3 involvement (i.e., WBC ≥ 5/μL in the cerebrospinal fluid with blasts present on cytospin)

PATIENT CHARACTERISTICS:

  • Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age) OR ECOG PS 0-2
  • Life expectancy ≥ 8 weeks
  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • Direct bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 2.5 times ULN (unless it is related to leukemic involvement)
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 45% by gated radionuclide study
  • No evidence of dyspnea at rest or exercise intolerance
  • Pulse oximetry > 94% at room air
  • Amylase ≤ 1.5 times ULN
  • Lipase < 1.5 times ULN
  • No active, uncontrolled grade 3 or 4 infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • No known hepatitis B or C infection or history of cirrhosis

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from all prior therapy*
  • At least 14 days since prior cytotoxic therapy (except hydroxyurea and intrathecal chemotherapy)*
  • At least 7 days since prior biologic agent*
  • At least 14 days since prior monoclonal antibody therapy*

  • No more than 1 prior autologous or allogeneic hematopoietic stem cell transplantation

    • No evidence of active graft-vs-host disease
    • At least 4 months since transplantation
  • No other concurrent chemotherapy or immunomodulating agents
  • No other concurrent investigational therapy NOTE: *Patients who relapse during ALL maintenance therapy do not require a waiting period.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clofarabine 40 mg/m² to assess feasibility in ALL patients.
Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 40 mg/m² to assess feasibility in AML patients.
Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 52 mg/m² to assess feasibility in ALL patients.
Clofarabine 52 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 52 mg/m² to assess efficacy in ALL patients.
Clofarabine 52 mg/m² to assess efficacy in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 52 mg/m² to assess feasibility in AML patients.
Clofarabine 52 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 52 mg/m² to assess efficacy in AML patients
Clofarabine 52 mg/m² to assess efficacy in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Experimental: Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
Clofarabine 52 mg/m² to assess efficacy in acute leukemia of ambiguous lineage patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.
Other: laboratory biomarker analysis
Drug: cytarabine
Given IV
Other Names:
  • Ara-C
  • Cytosar
  • Cytosine arabinoside
  • NSC #063878
Drug: clofarabine
Given IV for 5 days
Other Names:
  • Evoltra
  • Clolar
  • CAFdA
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
  • NSC# 606,869
  • IND # 73,789
Drug: methotrexate
Given intrathecally or IT age based dosage
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response (CR for ALL Patients), (CR + CRp for AML Patients)
Time Frame: 2 cycles or up to 84 days

Overall response for ALL patients: CR - complete remission (attainment of an M1 bone marrow (< 5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil count (ANC) > 750/μL and platelet count > 75,000/μL).

Overall response for AML patients: (CR + CRp), defined as:

CR - complete remission (attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral blood counts (absolute neutrophil count (ANC) > 1000/uL and platelet count > 100,000/uL)) or CRp - remission without platelet recovery (Attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of absolute neutrophil count (ANC) > 1000/uL and platelet transfusion independence (defined as: no platelet transfusions x 1 week)).
2 cycles or up to 84 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability as Measured by CTCAE v3.0
Time Frame: End of therapy
Number of participants with at least one grade 3 or higher adverse event during therapy.
End of therapy
Correlate the Expression of Apoptosis Specific Genes
Time Frame: End of therapy
Correlate the expression of apoptosis specific genes with chemoresistance and determine whether therapy with clofarabine is able to overcome blocks in apoptosis through modulation of gene expression. Gene expression analysis will be performed on specimens obtained during therapy. Apoptosis specific microarray data will be analyzed using GeneTraffic software (Iobion Informatics, La Jolla CA).
End of therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Bassem I. Razzouk, MD, St. Vincent Indianapolis Hospital
  • Study Chair: Todd Cooper, DO, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

September 6, 2006

First Submitted That Met QC Criteria

September 6, 2006

First Posted (Estimate)

September 7, 2006

Study Record Updates

Last Update Posted (Actual)

June 5, 2017

Last Update Submitted That Met QC Criteria

May 3, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAML0523
  • CDR0000494654 (Other Identifier: Clinical Trials.gov)
  • NCI-2009-00319 (Other Identifier: NCI Trial Identifier)
  • COG-AAML0523 (Other Identifier: Children's Oncology Group)

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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