T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00939653
Recruitment Status : Terminated (Study lost funding and it was decided that it could not meet it's accrual goals.)
First Posted : July 15, 2009
Last Update Posted : March 9, 2012
Genzyme, a Sanofi Company
Information provided by:
Therapeutic Advances in Childhood Leukemia Consortium

Brief Summary:

Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating children (age 1-21) with leukemia. This research study will use clofarabine with two other cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and cyclophosphamide (Cytoxan®).

Clofarabine, etoposide and cyclophosphamide have been used together in a phase I study to find out the highest doses of these drugs that can be safely given to children with relapsed or refractory leukemia. This study is a phase II study which will use the drugs to study how well these drugs work against AML. This study will also examine the safety of this drug combination.

Condition or disease Intervention/treatment Phase
Relapsed Acute Myelogenous Leukemia Drug: clofarabine Drug: etoposide Drug: cyclophosphamide Drug: filgrastim Drug: cytarabine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: T2007-002 A Phase II Study of Clofarabine With Etoposide and Cyclophosphamide in Relapsed/Refractory AML (IND 104,650)
Study Start Date : July 2009
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Intervention Details:
    Drug: clofarabine
    40 mg/m2/day IV over 2 hours (given at hours 0 to 2) on days 1 through 5.
    Other Name: Clolar
    Drug: etoposide
    100 mg/m2/day IV over 2 hours (given at hours 2 to 4) on days 1 through 5.
    Other Names:
    • VP-16
    • VePesid
    • Etopophos
    Drug: cyclophosphamide
    440 mg/m2/day IV as a 30-60 minute infusion (given at hours 4 to 5) on days 1 through 5.
    Other Name: Cytoxan
    Drug: filgrastim
    5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is > 1000 x 2 days.
    Other Names:
    • Neupogen
    • G-CSF
    • GCSF
    • Granulocyte Colony Stimulating Factor
    Drug: cytarabine
    Given intrathecally on day 1 at the dose defined by age below. 30 mg for patients age 1-1.99 50 mg for patients age 2-2.99 70 mg for patients >3 years of age
    Other Names:
    • Cytosine Arabinoside
    • Ara-C
    • Cytosar
    • AraC

Primary Outcome Measures :
  1. AML disease status after chemotherapy evaluated by bone marrow aspirates/biopsies and complete blood count. [ Time Frame: Between day 22 and 36 of course 1 and 2 ]

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: patients must be ≥ 1 and ≤ 21 years of age at the of study entry.
  • Diagnosis:

    • Patients must have a diagnosis of first or second relapse or refractory acute myelogenous leukemia (AML) according to WHO classification with ≥ 5% blasts in the bone marrow, with or without extramedullary disease. (See Appendix I)
    • Patients may have CNS 1 or CNS 2 disease but not CNS 3.
  • Performance Level: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age.
  • Prior Therapy:

    • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
    • Patient has not received more than 2 previous induction attempts. (Frontline therapy is included in this count).
    • Patients must have adequate venous access.
    • At least 1 year must have elapsed since hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD.
  • Reproductive Function

    • Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 2 weeks prior to enrollment.
    • Female patients with infants must agree not to breastfeed their infants while on this study.
    • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
  • Renal and Hepatic Function:

Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:

  • Patients must have a normal calculated creatinine clearance.
  • Total bilirubin <1.5 x ULN for age and conjugated/direct serum bilirubin ≤ ULN for age if total bilirubin is elevated.
  • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN.
  • Alkaline phosphatase ≤ 2.5 × ULN.

    • Informed Consent: Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent.
    • Protocol Approval: All institutional, FDA, and OHRP requirements for human studies must be met.

Exclusion Criteria:

  • Patients with Down Syndrome.
  • Prior treatment with Clofarabine.
  • Previous history of veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD, defined as: conjugated serum bilirubin > 1.4 mg/dL AND unexplained weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right upper quadrant pain without another explanation, OR reversal of portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.
  • Patients who have a history of cirrhosis of the liver or who are positive for hepatitis B core antibody (anti-HBc) or have a positive test for hepatitis C antibody (anti-HCV).
  • Patient has received TBI.
  • If it has been less than 1 year since the patient had a HSCT.
  • Infection Criteria

    • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
    • Positive blood culture within 48 hours of study registration.
    • Patient required supplemental oxygen or vasopressors within 48 hours of study (Oxygen after anesthesia for procedures is ok).
  • Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before planned drug initiation with the exception of hydroxyurea or intrathecal therapy given with the diagnostic lumbar puncture.
  • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
  • Pregnant or lactating patients.
  • Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  • Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:

    • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
    • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.

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 identifier (NCT number): NCT00939653

United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Stanford University Medical Center
Palo Alto, California, United States, 94304-1812
UCSF School of Medicine
San Francisco, California, United States, 94143-0106
United States, Florida
University of Miami Cancer Center
Miami, Florida, United States, 33136
United States, Illinois
Children's Memorial
Chicago, Illinois, United States
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0914
United States, Minnesota
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404-4597
United States, New York
New York University Medical Center
New York, New York, United States, 10016
United States, North Carolina
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
Genzyme, a Sanofi Company
Study Chair: Paul Gaynon, MD Children's Hospital Los Angeles
Study Chair: Nobuko Hijiya, MD Ann & Robert H Lurie Children's Hospital of Chicago

Additional Information:
Responsible Party: Paul Gaynon, MD, Therapeutic Advances in Childhood Leukemia Consortium Identifier: NCT00939653     History of Changes
Other Study ID Numbers: T2007-002
First Posted: July 15, 2009    Key Record Dates
Last Update Posted: March 9, 2012
Last Verified: March 2012

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:
Acute myelogenous leukemia
Relapsed AML

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic