Clofarabine for Relapsed or Refractory T-Cell or B-Cell Non-Hodgkin Lymphoma (NHL)

October 24, 2017 updated by: Dr. Sigrun Hallmeyer, Oncology Specialists, S.C.

A Phase I/II Open-label Study of Clofarabine in Patients With Relapsed or Refractory Diffuse Large Cell B-Cell NHL

This research is being done to develop new treatment for non-hodgkin's lymphoma in subjects whose cancer has returned or resisted treatment with chemotherapy. The investigational drug clofarabine is being used in this study. An investigational drug is one that has not been approved by the United States Food and Drug Administration (FDA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The safety profile of clofarabine appears acceptable within the target populations studied to date in the clinical studies, with numerous responses observed in heavily pre-treated patients with relapsed/refractory ALL or AML. Dose escalation of clofarabine in patients with solid tumors and lymphoproliferative disorders has been limited because grade 3 and 4 myelosuppression was considered acceptable in patients with acute leukemia, provided that hematologic recovery occurred within 6 weeks of therapy , and dose escalation has proceeded as high as 40 mg/m2 in this patient population. Furthermore, no responses were observed in a recent trial in which patients with relapsed CLL were treated with clofarabine 2 mg/m2, an indolent B-cell lymphoproliferative disorder indicating that low doses are likely to be ineffective in patients with aggressive NHL. (Personal Communication with ILEX Products, INC.)

This Phase I/II study will evaluate escalating doses of clofarabine in patients with relapsed and refractory diffuse large cell B-cell NHL starting at a dose of 4 mg/m2/day for 5 consecutive days and repeated every 28 days for a maximum of 6 cycles. This dosing regimen should be evaluated in this patient population because there is no standard therapy at relapse and grade 3 and 4 myelosuppression is frequently observed with traditional NHL salvage. Additionally, patients will receive granulocyte colony stimulating factors at the discretion of the investigator. Antifungal and antibacterial prophylaxis will be administered to minimize the risk of infection.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2
  • Phase 1

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
    • Illinois
      • Park Ridge, Illinois, United States, 60068
        • Oncology Specialists, SC

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:

  • Adult patients who are at least 18 years old with histology confirmed diffuse large cell B-cell NHL who have failed prior systemic chemotherapy with or without monoclonal antibody-based therapies.
  • Measurable disease determined by Ct or PET scans or bone marrow involvement, defined as lesions that can be accurately measured in two dimensions by CT or PET scan with the longest diameter accurately as greater than or equal to 1.0 cm or palpable lesions with both diameters greater than or equal to 2.0 cm. PET scan measurable disease is defined based on SUV value as determined by nuclear medicine evaluation.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0,1,or 2.
  • Life expectancy greater than 12 weeks.

  • Laboratory values obtained less than or equal to 14 days prior to registration:

    • Absolute neutrophil count (ANC) greater than or equal to 1500.
    • White blood cell (WBC) count greater than 3.0.
    • Platelets greater than or equal to 100.
    • Hemoglobin (HG) greater than 9.0 g/dL.
    • Total bilirubin less than or equal to 2.0 mg/dL.
    • Aspartate transaminase (AST)/alanine transaminase (ALT) less than or equal to 3 times the upper limit of normal (ULN). Higher values are acceptable if it is deemed that they are related to liver involvement with NHL.
    • Serum creatinine less than or equal to 2.0 mg/dL.
  • Cardiac function on pretreatment MUGA scan or echocardiogram that is considered normal by institutional standards.
  • 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 minium of 6 months after study treatment.

Exclusion Criteria:

  • Previously untreated NHL.
  • Received previous treatment with clofarabine.
  • History of T-cell lymphoma.
  • Bulky disease (ie, any single mass greater than 10 cm or circulating malignant cells greater than or equal to 24,000 cells/ul.
  • Patients with known AIDS-related or HIV-positive lymphoma.
  • Autologous bone marrow or stem cell transplant within 3 months of study entry.
  • History of allogeneic bone marrow transplant or organ transplant.
  • Prior radiotherapy to the only site of measurable disease.
  • Any medical condition that requires chronic use of oral high-dose corticosteroids. ( in excess of 1 mg/kg/day).
  • Autoimmune thrombocytopenia.
  • Use if investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
  • Patients with an 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 of parenteral antifungal therapy).
  • HIV-positive status.
  • Active secondary malignancy.
  • 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.
  • Patients with active or untreated central nervous lymphoma (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: 1
Clofarabine 4 mg/m^2 days 1-5 of every cycle for a maximum of 6 cycles.
Drug: CLOFARABINE
4 mg/m^2 days 1-5 of every cycle for a maximum of 6 cycles
Other Names:
  • Clolar®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I Maximum Tolerated Dose
Time Frame: days 1 -28, maximum 6 cycles
Maximum Tolerated Dose for Clofarabine. Cohorts of 3 patients each will receive doses of clofarabine increased in increments as follows: 4, 6, 8, 10, 12,…etc mg/m2/day for 5 days. The dose level immediately below the MTD will be used to treat patients in the Phase II part of the study. Starting dose of 4 mg/m2.
days 1 -28, maximum 6 cycles
Phase II Overall Response
Time Frame: 5 years
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity
Time Frame: 5 years
Number of Participants with Toxicity
5 years

Collaborators and Investigators

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

Sponsor

Oncology Specialists, S.C.

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: Chadi Nabhan, MD, Oncology Specialists,SC

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.

General Publications

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

September 1, 2005

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

November 29, 2017

Last Update Submitted That Met QC Criteria

October 24, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1066306 (0408)

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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