A Study of Clofarabine in Japanese Patients With Acute Myeloid 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: NCT01090167
Recruitment Status : Completed
First Posted : March 19, 2010
Last Update Posted : March 19, 2014
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief Summary:
This study is sponsored by Genzyme Japan K.K. The purpose of this study is to assess the safety, tolerability and pharmacokinetics of Clofarabine (JC0707) intravenously administered to Japanese adult patients with newly diagnosed or relapsed/refractory Acute Myeloid Leukemia (AML) at 20, 30, and 40 mg/m2/day on a 5-day dose schedule.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Drug: clofarabine Phase 1

Detailed Description:

This is a Phase I, open-label, multi-center study of Clofarabine administered to Japanese patients with Acute Myeloid Leukemia (AML) who are relapsed/refractory or elderly untreated AML for whom standard induction chemotherapy is unlikely to be of benefit.

Cohort 1 will receive 20 mg/m2/day of Clofarabine once daily for five consecutive days, Cohort 2 will receive 30 mg/m2/day, and Cohort 3 will receive 40 mg/m2/day. Patients will receive one cycle as a rule. However, if there is evidence of some hematologic response after one cycle of treatment with Clofarabine, patients may receive up to a maximum of three cycles. If patients fail to achieve CR or CRp after two cycles of treatment with Clofarabine, further dosing for such patients should be stopped.

Three patients constituting a cohort will receive Clofarabine and will then be assessed for dose limiting toxicities (DLT) at Cycle 1. If none of these three patients develops DLT, the next cohort will be introduced. If one of them develops DLT, three new patients will be added to the cohort, so that six patients in total are included in the tolerability assessment. In this case, treatment of the next cohort is allowed only in the case the number of patients who develop DLT is still one in this six-patient cohort. If two of the six patients develop DLT, however, the tolerability is ruled out. However, if two DLTs are observed at the 20mg/m2/day dose cohort, new patients will be enrolled at cohort -1 15mg/m2/day; and if no more than one of six patients in the cohort develop DLT, it will be considered as the last cohort for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Multi-center Study of Clofarabine (JC0707) in Japanese Patients With Acute Myeloid Leukemia (AML)
Study Start Date : February 2010
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Arm Intervention/treatment
Experimental: Clofarabine Drug: clofarabine
Intravenous, 20 mg/m2, 30 mg/m2, 40 mg/m2
Other Name: Evoltra, Clolar, JC0707

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) as determined by Dose Limiting Toxicities (DLTs) [ Time Frame: 28 days (1st cycle) ]
  2. Safety as measured by number of patients with at least one adverse events (incidence) [ Time Frame: 50 days ]
  3. Safety as measured by severity of adverse events [ Time Frame: 50 days ]
  4. Safety as measured by duration of adverse events [ Time Frame: 50 days ]
  5. Safety as measured by causality of adverse events [ Time Frame: 50 days ]
  6. Safety as measured by seriousness of adverse events [ Time Frame: 50 days ]
  7. Safety as measured by type of adverse event [ Time Frame: 50 days ]
  8. Safety as measured by number of deaths [ Time Frame: 50 days ]
  9. Safety as measured by number of serious adverse events [ Time Frame: 50 days ]
  10. Safety as measured by number of patients who discontinue due to adverse events [ Time Frame: 50 days ]
  11. Safety as measured by clinically significant changes in hematology [ Time Frame: 50 days ]
  12. Safety as measured by clinically significant changes in chemistry parameters (i.e. serum chemistry) [ Time Frame: 50 days ]
  13. Pharmacokinetic (PK) parameters (Cmax, Tmax, AUC) [ Time Frame: 6 days ]

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Ages Eligible for Study:   20 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients having diagnosis of relapsed or refractory Acute Myeloid Leukemia (AML) according to the World Health Organization (WHO) criteria or untreated AML patients (60 years to 74 years) for whom standard induction chemotherapy is unlikely to be of benefit as judged by the investigator (or co-investigator)
  • Age at the time of informed consent 20 years up to 74 years; 60 years or older for patients with previously untreated AML
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Be able to comply with the study procedures and follow-up examinations specified in this protocol.
  • Hepatic, renal, pancreatic, and cardiac function satisfying the laboratory values criteria

Exclusion Criteria:

  • Patients having diagnosis of acute promyelocytic leukemia(APL, French-American-British classification M3 or WHO classification of APL with t(15;17)(q22;q12), (PML/RARA and variants)
  • Have had prior hematologic stem cell transplant
  • Have had prior external beam radiation therapy to the pelvis
  • Have systemic fungal, bacterial, viral, or other infection that cannot be controlled and is exhibiting symptoms related to the infection despite appropriate treatment. In addition, patients must have a temperature less than 38.0 for at least 48 hours prior to the first dose of the study drug.
  • Have any other severe concurrent disease that is difficult to control by drug therapies, or have a history of serious organ dysfunction or disease involving the liver, kidney, pancreas, heart, or other organ system that may place the patient at undue risk
  • Diagnosis of another malignancy, unless the patient meets none of the following conditions: 1) Any persisting treatment-related adverse events; 2) Less than 180 days of disease-free duration counted during the period from the treatment completion to enrollment; note that the patients meeting any of the following conditions is eligible:
  • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia are eligible for this study if 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.
  • Have a prior positive test for HBs antigen or antibody, HBc antibody, HCV antibody, or HIV antigen or antibody; note that the patients who have had treatment of vaccine and positive for HBs antibody is eligible.
  • Have a clinically significant arrhythmia at screening or a known family history of QT prolongation. Marked prolongation of QTc interval exceeding 450 msec is considered clinically significant
  • Have clinical evidence suggestive of central nervous system (CNS) involvement with leukemia
  • Have a Psychiatric disorders that would interfere with consent, study participation, or follow-up
  • Have had prior treatment with the study drug
  • Have had any other chemotherapy or investigational agent received within 30 days prior to the first dose of the study drug
  • If received any chemotherapy or investigational agent prior to this time point, drug-related adverse events must be recovered to the baseline value or Grade 1 or less prior to the first dose of the study drug (except for alopecia, and nail changes).
  • Is currently participating in another concurrent investigational protocol
  • Are pregnant or lactating.
  • Male and female patients who are fertile must agree to use an effective means of birth control to avoid pregnancy during the study period and for six months after the last dose of study drug.

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): NCT01090167

Nagoya Daini Red Cross Hospital
Aichi, Japan
National Hospital Organization Nagoya Medical Center
Aichi, Japan
University of Fukui Hospital
Fukui, Japan
Tokai University Hospital
Kanagawa, Japan
Jichi Medical University Hospital
Tochigi, Japan
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
Tokyo, Japan
Sponsors and Collaborators
Genzyme, a Sanofi Company
Study Director: Medical Monitor Genzyme, a Sanofi Company

Responsible Party: Genzyme, a Sanofi Company Identifier: NCT01090167     History of Changes
Other Study ID Numbers: CLOAML10508
First Posted: March 19, 2010    Key Record Dates
Last Update Posted: March 19, 2014
Last Verified: March 2014

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents