Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

NCT01101880 | Completed Phase 2 Results

• 2 other identifiers: 7144NCI-2010-00282
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial is studying how well giving clofarabine and cytarabine together with filgrastim works in treating patients with newly diagnosed acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS), and/or advanced myeloproliferative neoplasm. 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. Giving the drugs in different doses may kill more cancer cells. Colony stimulating factors, such as filgrastim, 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.

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

Outcome Measures

Primary Outcomes (6)

• Rates of Complete Remission and Complete Remission With Incomplete Recovery of Counts

  With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. Complete remission is defined as less than 5% blast cells present in the bone marrow and count recovery (absolute neutrophil count greater than 1000/microL and platelet count greater than 100,000/microL). Complete remission with incomplete recovery of counts is defined as less than 5% blast cells present in the bone marrow without compete count recovery (absolute neutrophil count less than 1000/microL and platelet count less than 100,000/microL).

  Up to 5 years

• Duration of Remission

  With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates. Remission is defined as less than 5% blasts in the bone marrow, no appearance of blasts in the peripheral blood, and no extramedullary disease (appearance of leukemic cells in other tissues).

  Up to 5 years

• Time to Progression

  With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates.

  Up to 5 years

• Event Free Survival

  Number of patients in remission at a median follow up of 15 months.

  Up to 5 years

• Treatment-related Mortality (TRM)

  Treatment-related mortality (TRM) data was not collected.

  Up to 5 years

• Overall Survival

  With 50 patients, the rates of these endpoints will be estimated with a standard error of 5 to 7 percentage points, depending on the observed rates.

  Up to 5 years

Study Arms (1)

Treatment (chemotherapy and colony stimulating factor)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive filgrastim SC daily beginning the day prior to chemotherapy and continuing until blood counts recover. Patients receive clofarabine IV over 1 hour followed by cytarabine IV over 2 hours daily for 5 days. CONSOLIDATION THERAPY: Patients receive filgrastim SC daily for 5 days beginning the day prior to chemotherapy. Patients receive clofarabine IV over 1 hour followed by cytarabine IV over 2 hours daily for 4 days. Treatment with induction therapy may continue for up to 2 courses and treatment with consolidation therapy may continue for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Biological: filgrastim; Drug: clofarabine; Drug: cytarabine

Interventions

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Treatment (chemotherapy and colony stimulating factor)

clofarabine DRUG

Given IV

Also known as: CAFdA, Clofarex, Clolar

Treatment (chemotherapy and colony stimulating factor)

cytarabine DRUG

Given IV

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

Treatment (chemotherapy and colony stimulating factor)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of acute myeloid leukemia by World Health Organization (WHO) criteria (except acute promyelocytic leukemia), or myelodysplastic syndrome, RAEB-2 by WHO classification or advanced myeloproliferative neoplasm with \>= 10% blasts in the bone marrow or peripheral blood, including chronic myelomonocytic leukemia (CMML)-2 by WHO classification
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
• 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 as calculated by the Modification of Diet in Renal Disease equation
• Serum bilirubin =\< 1.5 x upper limit of normal (ULN) unless elevation is thought to be due to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic malignancy
• Aspartate transferase (AST)/alanine transferase (ALT) =\< 2.5 x ULN unless elevation is thought to be due to hepatic infiltration by the hematologic malignancy
• Alkaline phosphatase =\< 2.5 x ULN
• 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 use an effective contraceptive method during the study and for a minimum of 90 days after study treatment

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol with the exception of intrathecal chemotherapy administered on days that are not concurrent with clofarabine and cytarabine
• No prior induction chemotherapy for AML; treatment with hydroxyurea is permitted; treatment with imides or hypomethylating agents for preceding hematological disorders is permitted
• 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 significant organ compromise due to systemic fungal, bacterial, viral, or other infection
• Pregnant or lactating patients
• Any significant concurrent illness, condition, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
• Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy including the following:
• Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive 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
• Prior allogeneic stem cell transplant

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Becker PS, Medeiros BC, Stein AS, Othus M, Appelbaum FR, Forman SJ, Scott BL, Hendrie PC, Gardner KM, Pagel JM, Walter RB, Parks C, Wood BL, Abkowitz JL, Estey EH. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol. 2015 Apr;90(4):295-300. doi: 10.1002/ajh.23927. Epub 2015 Jan 30.

  PMID: 25545153 DERIVED

MeSH Terms

Conditions

Congenital Abnormalities; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Clofarabine; Cytarabine

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

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; 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

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 2
• 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: April 8, 2010
• First Posted: April 12, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: July 1, 2017
• Last Updated: October 19, 2017
• Results First Posted: October 19, 2017

Record last verified: 2017-09

Locations

US (3)