Brief Title
Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
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
Brief Summary
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 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 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
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of clofarabine, and the dose-limiting toxicities
of the combination of clofarabine and cytarabine with G-CSF priming, in the treatment of
patients with relapsed or refractory AML.
SECONDARY OBJECTIVES:
I. To determine the hematological and non-hematological side effect profile of the
combination of clofarabine, cytarabine, and G-CSF.
II. To determine the efficacy of clofarabine in combination with cytarabine and G-CSF priming
in the treatment of patients with relapsed or refractory AML.
III. 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 I:
INDUCTION THERAPY: Patients receive 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 count recover. Patients with residual leukemia (>= 5%
blasts by morphology) at day 14 and if blast remain > 5% by day 21 receive a second course of
induction therapy.
CONSOLIDATION THERAPY: Patients receive clofarabine, 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.
PARTS II and III:
Patients receive induction therapy and consolidation therapy as in part 1.
After completion of study treatment, patients are followed every 3 months for 2 years and
then annually for 3 years.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Maximum Tolerated Dose of Clofarabine
Secondary Outcome
Hematologic and Non-hematologic Side Effect Profile
Condition
Acute Myeloid Leukemia
Intervention
clofarabine
Study Arms / Comparison Groups
Arm I
Description: See Detailed Description
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
50
Start Date
December 2007
Completion Date
April 2015
Primary Completion Date
March 2010
Eligibility Criteria
Inclusion Criteria:
- ECOG performance status 0-2
- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent
- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment
- Male and female patients must be willing to use an effective contraceptive method
during the study and for a minimum of 6 months after study treatment
- Serum Total or Direct bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 times ULN
- Diagnosis of acute myeloid leukemia by WHO criteria, either relapsed or refractory;
acute promyelocytic leukemia [acute promyelocytic leukemia with t(15;17)(q22;q12) and
variants] would be eligible only after failure of a regimen containing arsenic
trioxide
- 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 m^2
- Alkaline phosphatase =< 2.5 times ULN
Exclusion Criteria:
- Use of investigational agents within 30 days or initiation of any other anticancer
therapy within 2 weeks before study entry with the exception of hydroxyurea, and
intrathecal therapy for leukemic meningitis
- 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)
- Pregnant or lactating patients
- Any 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
- Have any other severe concurrent disease, history of serious organ dysfunction, or
disease involving the heart, kidney, liver (including symptomatic hepatitis,
veno-occlusive disease, or hepatic graft-versus-host disease [for acute >= grade 2]),
or other organ system dysfunction
- No concomitant cytotoxic therapy or investigational therapy is allowed during the
study with the exception of intrathecal therapy for leukemic meningitis; intrathecal
therapy must not be given during or within 24 hours of any 5 day
Clofarabine/Cytarabine treatment period
- To the extent possible, use of nephrotoxic (e.g., vancomycin, amphotericin B, etc) and
hepatotoxic (e.g., voriconazole, cyclosporine, etc) agents is to be avoided during
clofarabine; use of alternative medications (e.g., herbal or botanical for anticancer
purposes) is not permitted during the entire study period
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol
- More than two failed induction attempts for initial diagnosis or current relapse; for
patients enrolled under part III of the protocol, patients must be at first salvage
after relapse less than one year from complete remission, or salvage after initial
induction chemotherapy
- Allogeneic transplant recipients on immunosuppression or on treatment for GVHD
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Pamela Becker, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00602225
Organization ID
6562
Secondary IDs
NCI-2009-01464
Responsible Party
Principal Investigator
Study Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Pamela Becker, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
February 2018