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

NCT00602225 | Completed Phase 1 Results

• 2 other identifiers: 6562NCI-2009-01464
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Myeloid Leukemia; 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

Outcome Measures

Primary Outcomes (6)

• Maximum Tolerated Dose of Clofarabine

  45 days after the last dose of clofarabine

• Dose-limiting Toxicity as Assessed by NCI CTCAE v3.0

  45 days after the last dose of clofarabine

• Response Rates by Cytogenetic Risk Category

  Number of participants who achieved Complete Remission (less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) under each cytogenetic risk category.

  45 days after the last dose of clofarabine

• Response Rates by Cytogenetic Risk Category and Clofarabine Dose

  Number of participants under each Cytogenetic Risk Category and Clofarabine dose who achieve CR (Complete Remission = less than 5% blasts in the marrow and count recovery of Absolute Neutrophil Count to 1,000/microL and Platelet Count to 100,000/microL) or CRp (Complete Remission, but with a platelet count of less than 100,000/microL).

  45 days after the last dose of clofarabine

• Response Rates by Duration First Complete Remission (CR1)

  Number of participants whose first Complete Remission lasted 0, 1-6, 6-12, or greater than 12 months. Only those participant who had a first CR are included in this data.

  45 days after the last dose of clofarabine

• Response Rates by Salvage Number

  Number of participants in each Salvage number category who achieved a Complete Remission. Salvage number refers to whether treatment with GCLAC on this study was the pariticipant's first salvage regimen (1), second salvage regimen (2), or third or greater salvage regimen (3 or greater).

  45 days after the last dose of clofarabine

Secondary Outcomes (4)

• Hematologic and Non-hematologic Side Effect Profile

  45 days after the last dose of clofarabine

• Efficacy

  At five years after the last dose of clofarabine

• Disease-free Survival

  At five years after the last dose of clofarabine

• Overall Survival

  At five years after the last dose of clofarabine

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

Drug: clofarabine; Drug: cytarabine; Biological: filgrastim

Interventions

clofarabine DRUG

Given IV

Also known as: CAFdA, Clofarex, Clolar

Arm I

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I

filgrastim BIOLOGICAL

Given subcutaneously

Also known as: G-CSF, Neupogen

Arm I

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Becker PS, Kantarjian HM, Appelbaum FR, Storer B, Pierce S, Shan J, Faderl S, Estey EH. Retrospective comparison of clofarabine versus fludarabine in combination with high-dose cytarabine with or without granulocyte colony-stimulating factor as salvage therapies for acute myeloid leukemia. Haematologica. 2013 Jan;98(1):114-8. doi: 10.3324/haematol.2012.063438. Epub 2012 Jul 16.

  PMID: 22801963 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Promyelocytic, Acute

Interventions

Clofarabine; Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Pamela Becker, MD, PhD
• Organization: University of Washington

pbecker@uw.edu

206-288-7273

Study Officials

• Pamela Becker

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 23, 2008
• First Posted: January 28, 2008
• Study Start: December 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: April 1, 2015
• Last Updated: March 9, 2018
• Results First Posted: September 8, 2017

Record last verified: 2018-02

Locations

US (1)