A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kristie Blum, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00201669
First received: September 12, 2005
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

This study will determine the efficacy of clofarabine as measured by response rate in patients with aggressive non-Hodgkin's lymphoma


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Clofarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Clofarabine in Patients With Aggressive Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate [ Time Frame: up to two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the toxicity of clofarabine administered in conjunction with growth factor support in patients with relapsed/refractory aggressive NHL. [ Time Frame: up to two years ] [ Designated as safety issue: Yes ]
  • determine the effect of clofarabine on T-, B-, and natural killer (NK)-cell subsets and quantitative immunoglobulin levels after prolonged administration of clofarabine in patients with NHL. [ Time Frame: up to two years ] [ Designated as safety issue: No ]
  • Assess cytokine (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and IL-10) release following clofarabine therapy. [ Time Frame: up to two years ] [ Designated as safety issue: No ]
  • Assess the effect of pre-treatment prognostic factors (p53 mutational status, DNA methylation, and apoptotic protein levels) in patient-derived tumor tissue on response to clofarabine. [ Time Frame: up to two years ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: October 2004
Study Completion Date: June 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Clofarabine
    40 mg/m2/day will be administered as a 2 hour intravenous infusion (IVI) on days 1-5
    Other Name: Clolar
Detailed Description:

Rationale: Two Food and Drug Administration drugs approved for blood cancers such as non-Hodgkin's lymphoma (NHL) include fludarabine (Fludara) and cladribine (Leustat). The drug offered in the current study, clofarabine was designed to combine the anti-cancer strength of both fludarabine and cladribine. Laboratory research suggests that clofarabine targets anti-cancer mechanisms in cells, helps repair DNA, and inhibits tumor growth. Research also indicates that clofarabine has some efficacy against a variety of blood cancers and solid tumors. Numerous tumor responses have been observed with high doses of clofarabine in heavily pretreated patients with different types of lymphoma. The current study build on this previous research to test clofarabine in patients with aggressive NHL.

Purpose: This study will evaluate the safety and efficacy of clofarabine for aggressive NHL. Toxicities resulting from the combination of clofarabine and the supportive care drug GM-CSF will also be analyzed in patients. GM-CSF is a blood-forming agent that stimulates the production of white blood cells. In addition, several tests, including blood and tumor tissue analysis, will assess immune response and biological changes to the tumor as a result of study drugs.

Treatment: Patients in this study will be given clofarabine through intravenous infusions. This drug will initially be provided to patients for five consecutive days. Several tests will then be conducted and supportive care agents will be administered to stabilize patients' blood cell counts, immune response, and reduce the risk of infection. The first ten patients in this study will be hospitalized until recovery from the first five days of clofarabine to carefully monitor any additional toxicities resulting from the dosing regimen. Patients will receive another five day treatment cycle with clofarabine within seven days after recovering from each previous cycle and no more than four weeks from the start of the previous cycle. Disease response will be measured after every two cycles of treatment with clofarabine. Patient with stable or reduced disease will receive a maximum of six treatment cycles with clofarabine. Treatments will be discontinued due to disease growth, unacceptable side effects, or a treatment delay of more than 21 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have histologically confirmed aggressive NHL
  • B-cell NHL must be relapsed/ refractory
  • T-cell & NK-cell and transformed lymphoma eligible at DX
  • Patients with B-cell NHL (ie, diffuse large B-cell lymphoma, mantle cell lymphoma, and Burkitt's lymphoma) must have relapsed or refractory disease after at least 1 prior therapy.
  • Patients previously treated with radioimmunotherapy (ie, ibritumomab tiuxetan [Zevalin] or tositumomab [Bexxar]) or prior stem cell transplant (SCT) are eligible.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Life expectancy of at least 12 weeks.
  • Laboratory values obtained ≤ 7 days prior to registration:

    • Absolute neutrophil count (ANC) ≥ 1500/mm3
    • Platelets ≥ 100,000/mm3
    • Total bilirubin ≤ upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2 × ULN
    • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2 × ULN
    • Serum creatinine ≤ ULN

Exclusion Criteria:

  • No prior treatment with clofarabine.
  • Full recovery from all acute toxicities associated with prior chemotherapy, radiotherapy, or immunotherapy.- Patients with active, uncontrolled systemic infection considered to be opportunistic, life threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients on parenteral antifungal therapy) are not eligible.
  • Cardiac function (i.e. left ventricular ejection fraction) ≥ 50% on pretreatment radionuclide ventriculography (RVG) or echocardiogram.
  • Women that are pregnant or breastfeeding.
  • Known HIV disease.
  • No CNS lymphoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00201669

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Kristie Blum
Investigators
Principal Investigator: Kristie Blum Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Kristie Blum, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00201669     History of Changes
Other Study ID Numbers: OSU-0442
Study First Received: September 12, 2005
Last Updated: May 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Aggressive
Clofarabine

Additional relevant MeSH terms:
Aggression
Lymphoma
Lymphoma, Non-Hodgkin
Behavioral Symptoms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Clofarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014