Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00602225

Purpose

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. Colony stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine to see how well it works when given together with cytarabine and G-CSF in treating patients with relapsed or refractory acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Drug: clofarabine Drug: cytarabine Drug: filgrastim	Phase I Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Filgrastim Cytarabine Cytarabine hydrochloride Granulocyte colony-stimulating factor Clofarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Dose Escalation Study of Clofarabine in Combination With Cytarabine (Ara-C) and G-CSF Priming for Relapsed or Refractory Acute Myeloid Leukemia (AML) Patients

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of clofarabine [ Designated as safety issue: Yes ]
Dose-limiting toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Hematologic and non-hematologic side effect profile [ Designated as safety issue: Yes ]
Efficacy [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	19
Study Start Date:	January 2008
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the maximum tolerated dose of clofarabine, and the dose-limiting toxicities of the combination of clofarabine and cytarabine with filgrastim (G-CSF) priming, in the treatment of patients with relapsed or refractory acute myeloid leukemia (AML).

Secondary

To determine the hematological and non-hematological side effect profile of the combination of clofarabine, cytarabine, and G-CSF.
To determine the efficacy of clofarabine in combination with cytarabine and G-CSF priming in the treatment of patients with relapsed or refractory AML.
To determine the disease-free and overall survival after therapy with clofarabine, cytarabine, and G-CSF for relapsed or refractory AML.

OUTLINE: This is a dose-escalation study of clofarabine.

Part 1:
- Induction therapy: Patients receive escalating doses of clofarabine IV over 1 hour and cytarabine IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously once daily beginning 24 hours prior to chemotherapy and continuing until blood counts recover. Patients with residual leukemia (≥ 5% blasts by morphology) at day 14 and if blasts remain greater than 5% by day 21 receive a second course of induction therapy.
- Consolidation therapy: Patients then receive clofarabine (at a dose 5 mg/m² lower than the induction dose), cytarabine, and G-CSF as in induction therapy. Patients may receive a second course of consolidation therapy depending on response and whether additional therapy (e.g., stem cell transplant or donor lymphocyte infusion) is planned.
Part 2: Patients receive induction therapy as in part 1(with clofarabine at the maximum tolerated dose determined in part 1 induction therapy) and consolidation therapy as in part 1 (with clofarabine at a dose 5 mg/m² lower than the maximum tolerated dose).

After completion of study treatment, patients are followed every 3 months for 2 years and then annually for 3 years.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of acute myeloid leukemia by WHO criteria
- Relapsed or refractory disease
- Acute promyelocytic leukemia with t(15;17)(q22;q12) and variants allowed only after failure of a regimen containing arsenic trioxide
No more than two failed induction attempts for initial diagnosis or current relapse

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Creatinine ≤ 1.0 mg/dL or glomerular filtration rate > 60 mL/min
Serum bilirubin ≤ 1.5 mg/dL times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
No other severe concurrent disease
No history of serious organ dysfunction or disease involving the heart, kidney, liver (including symptomatic hepatitis, veno-occlusive disease, or at least grade 2 acute hepatic graft-versus-host disease), or other organ system dysfunction
No 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)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during the study and for a minimum of 6 months after study treatment
No significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results

PRIOR CONCURRENT THERAPY:

No other concurrent chemotherapy, radiotherapy, or immunotherapy
No investigational agents within the past 30 days
No anticancer therapy within the past 2 weeks (except for hydroxyurea and intrathecal therapy for leukemic meningitis)
- No intrathecal therapy within 24 hours of or during any 5 day treatment period with clofarabine/cytarabine
No concurrent cytotoxic or investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602225

Locations

United States, Washington
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Pamela S. Becker, MD, PhD

University of Washington

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	University of Washington School of Medicine ( Pamela S. Becker )
Study ID Numbers:	CDR0000584639, UWCC-6562, UWCC-UW 6562, UWCC-07-9655-H/A
Study First Received:	January 23, 2008
Last Updated:	December 31, 2008
ClinicalTrials.gov Identifier:	NCT00602225
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)

adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute promyelocytic leukemia (M3)
recurrent adult acute myeloid leukemia

Study placed in the following topic categories:

Clofarabine
Leukemia
Acute promyelocytic leukemia
Acute myelogenous leukemia
Leukemia, Promyelocytic, Acute
Acute myeloid leukemia, adult

Leukemia, Myeloid
Congenital Abnormalities
Leukemia, Myeloid, Acute
Acute myelocytic leukemia
Cytarabine
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents

Physiological Effects of Drugs
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses

ClinicalTrials.gov processed this record on January 14, 2009