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

December 4, 2017 updated by: Ohio State University Comprehensive Cancer Center
This study will determine the efficacy of clofarabine as measured by response rate in patients with aggressive non-Hodgkin's lymphoma

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Drug: Clofarabine
Clofarabine 30 mg/m2/day will be administered as a 2-hour intravenous infusion (IVI) on days 1-5.
Other Names:
  • Clolar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate
Time Frame: up to two years
up to two years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
up to two years
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
up to two years
Assess cytokine (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6, and IL-10) release following clofarabine therapy.
Time Frame: up to two years
up to two years
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
up to two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ohio State University Comprehensive Cancer Center

Investigators

  • Principal Investigator: Kristie Blum, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

May 1, 2006

Study Completion (Actual)

June 1, 2006

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Actual)

December 6, 2017

Last Update Submitted That Met QC Criteria

December 4, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-0442

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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