PK Study of Oral and IV Clofarabine in High Risk Myelodysplasia+Acute Leukemias

NCT01169012 | Completed Phase 1 DMC

• 2 other identifiers: LCCC 090910-0256
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-blinded, non-randomized pharmacokinetic study to determine the oral bioavailability of clofarabine, and the effect of cimetidine on clofarabine pharmacokinetics in patients with poor-risk acute leukemias and myelodysplastic syndrome (MDS).

Conditions

Myelodysplastic Syndrome; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelomonocytic Leukemia

Keywords

Myelodysplastic syndrome; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic myelomonocytic leukemia; Clofarabine; Clolar; University of North Carolina at Chapel Hill; Lineberger Comprehensive Cancer Center

Outcome Measures

Primary Outcomes (1)

• Define human intra-patient bioavailability of clofarabine; Compare the pharmacokinetics of intravenously-administered clofarabine when administered alone, with the pharmacokinetics of clofarabine when co-administered with cimetidine, an OCT2 inhibitor.

  Regarding primary endpoints, each patient will generate pharmacokinetic data sufficient to compute area under the concentration versus time curve (AUC) and clearance (Cl) for each of the initial three clofarabine doses (IV, PO and IV administered after cimetidine) for each patient. These values will be used to compute the human oral bioavailability of clofarabine and compare AUC and Cl of clofarabine when given after cimetidine with AUC and Cl of clofarabine when administered alone

  4 years

Secondary Outcomes (3)

• Examine safety of orally-administered clofarabine; Examine the safety of a combined intravenous and oral clofarabine regimen

  5 Years

• Examine efficacy of orally-administered clofarabine

  5 years

• Explore the influence of OCT2-encoding single nucleotide polymorphisms on clofarabine pharmacokinetics and pharmacodynamics

  5 years

Study Arms (1)

Single Arm Trial

OTHER

Single Arm Trial

Drug: Clofarabine

Interventions

Clofarabine DRUG

Intravenous Clofarabine (10mg/m2) Oral clofarabine (30mg/m2) Cimetidine (800mg)

Also known as: Clolar (intravenous clofarabine), Tagemet

Single Arm Trial

Eligibility Criteria

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

You may qualify if:

• MDS patients age 18 and older with IPSS risk of intermediate-2 who have failed ≥ 1 prior regimen with a DNA methyltransferase inhibitor, or have ≥ 10% bone marrow myeloblasts
• MDS patients age 18 and older with IPSS high risk
• Patients with CMML (chronic myelomonocytic leukemia) age 18 and older
• Untreated AML or Ph-negative ALL patients age 60 and over who are deemed not to be candidates for intensive anthracycline based induction therapies based on age, organ function or co-morbidities
• AML or Ph-negative ALL patients age 60 and over who have failed or relapsed following initial induction therapy
• Provide signed written informed consent.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
• 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 as calculated by the Cockcroft-Gault equation:
• GFR (mL/min) = (140 - age) X (weight in kg) X (0.85 if female)/ 72 X serum creatinine in mg/mL
• Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transaminase (ALT) \</=2.5 × ULN
• Alkaline phosphatase 2.5 × ULN
• Female patients of childbearing potential must have a negative serum pregnancy test within 1 week prior to enrollment.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. 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).
• 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.
• Abnormal organ function as defined by ALT, AST or total bilirubin \>1.5 x ULN, GFR\< 60mL/minute by MDRD equation
• Active cardiac disease as manifest by: \>class II NYHA congestive heart failure, unstable angina or myocardial infarction within the last 6 months
• Hemorrhage or bleeding \>/= CTCAE grade 3 within 4 weeks of enrollment
• Pulmonary hemorrhage \>/= CTCAE grade 2 within 4 weeks of enrollment
• HIV infection
• Active Hepatitis B or Hepatitis C infection (defined as measurable viral load by PCR, or liver function abnormalities attributed to viral hepatitis)
• Cerebrovascular accident or transient ischemic attack within 6 months of study enrollment.
• Non-healing wound or ulcer, or major surgery or trauma within 4 weeks of study enrollment
• Active graft versus host disease of any grade

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• Lineberger Comprehensive Cancer Center Home Page
• Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelomonocytic, Chronic

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Matthew Foster, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 23, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: January 1, 2013
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

US (1)