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Trial record 1 of 1 for:    NCT00727766
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Oral Clofarabine for Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00727766
First received: July 30, 2008
Last updated: November 10, 2014
Last verified: November 2014
  Purpose

This is a phase I study designed to test the safety of oral clofarabine when given as consolidation therapy to older patients with AML in remission.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Drug: Clofarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Oral Clofarabine Consolidation in Adults Aged 60 and Older With Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and dose limiting toxicity (DLT) [ Time Frame: DLT - 1st cycle (28 days), MTD - completion of 1st cycle by all patients in all cohorts ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adverse events by grade and attribution [ Time Frame: Start of treatment through 30 days post-last dose ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: Every 6 months for 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Every 6 months for 3 years ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: January 2009
Study Completion Date: November 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Clofarabine 1 mg for 14 days followed by 14 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar
Experimental: Cohort 2
Clofarabine 2 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar
Experimental: Cohort 3
Clofarabine 3 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar
Experimental: Cohort 4
Clofarabine 4 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar
Experimental: Cohort 5
Clofarabine 5 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar
Experimental: Cohort 6
Clofarabine 6 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.
Drug: Clofarabine
Other Name: Clolar

Detailed Description:

The prognosis of acute myeloid leukemia (AML) in patients 60 and older is dismal with traditional therapy. Several factors contribute to the poor prognosis of older individuals, including the increased incidence of the multidrug resistance efflux pump, comorbidities and unfavorable cytogenetics. The recently reported AML-13 and ALFA trials suggest that less intense consolidation in this population is at least equivalent to more intense, induction style efforts.

Clofarabine is a next generation nucleoside analogue that was designed to optimize the favorable attributes of fludarabine and cladribine, while minimizing toxicity. The intravenous formulation has shown considerable activity in older patients with AML who have been considered either unfit for or unlikely to benefit from conventional therapy. Additionally, clofarabine has an oral formulation that patients may find more acceptable for consolidation therapy rather than multiple courses of intravenous medications, administered over several days.

This study is designed as a traditional 3x3 phase I trial with the intention of defining the maximum tolerated dose of oral clofarabine consolidation for older patients with AML in remission.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Acute Myeloid Leukemia according to WHO criteria
  • Age ≥ 60 years at enrollment
  • Patients must be in complete remission by bone marrow examination, within 30 days of enrollment, following treatment with a cytotoxic induction chemotherapy regimen (such as 7+3)

    • Complete remission must be confirmed by bone marrow biopsy
    • If one cycle of consolidation was administered, then patient may be within 60 days of the confirmation of complete remission by bone marrow biopsy
    • Minimum platelet count of 100,000
  • Patients may have received "low-intensity" therapy (i.e. decitabine, lenalidomide, etc) prior to traditional induction chemotherapy.
  • Patients may have received 1 cycle of cytarabine-based consolidation therapy.
  • Patients must have an ECOG performance status of 0-2 at the beginning of consolidation therapy.
  • Have adequate renal and hepatic functions as indicated by the following laboratory values:

    • Serum creatinine ≤ 1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
    • Serum total bilirubin ≤ 1.5 mg/dL × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia secondary Gilbert's syndrome
    • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN
    • Alkaline phosphatase ≤ 2.5 × ULN
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide signed valid written informed consent or when appropriate, have an appointed legally authorized representative who is capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide signed valid written informed consent for the benefit of the patient.
  • Male and female patients who are of child bearing potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
  • Patients MAY have received prior therapy with purine analogs (such as fludarabine and cladribine).

Exclusion Criteria:

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • The diagnosis of AML-M3 (acute promyelocytic leukemia) characterized by translocations involving the retinoic acid receptor-alpha (RAR-alpha) gene.
  • Use of investigational agents within 2 weeks or any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
  • 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.
  • 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).
  • Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00727766

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Camille N. Abboud, M.D. Washington Univerisity
  More Information

Additional Information:
No publications provided by Washington University School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00727766     History of Changes
Other Study ID Numbers: 08-0853 / 201108049
Study First Received: July 30, 2008
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Clofarabine
Clolar
AML
Consolidation

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

ClinicalTrials.gov processed this record on November 27, 2014