Phase I Trial of Clofarabine in Combo w/ HD Etoposide & Cyclophosphamide and APBSCT for Pts w/ High-Risk or Refractory NHL

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00477945
First received: May 22, 2007
Last updated: March 30, 2012
Last verified: September 2011
  Purpose

This is a phase I trial to determine the maximum tolerated dose (MTD) of clofarabine in a combination with high-dose etoposide and cyclophosphamide. This is an initial step in developing a novel myeloablative preparative regimen for autologous hematopoietic stem cell transplantation (ASCT). While this phase I trial will initially develop the regimen in patients with refractory disease, it is expected that it will find its best application in patients with less advanced disease.


Condition Intervention Phase
Non Hodgkin's Lymphoma
Drug: clofarabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Clofarabine in Combination With High-Dose Etoposide and Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation for Patients With High-Risk or Refractory Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Determine the maximum tolerated dose (MTD) of clofarabine in association with high-dose etoposide and cyclophosphamide followed by ASCT in patients with refractory lymphoma malignancies. [ Time Frame: 1 yr ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of the toxicity of the combination of clofarabine, and high-dose etoposide and cyclophosphamide-- Describe engraftment kinetics-- Describe the response rate-- Describe relapse rate and event-free survival-- Assess clofarabine p [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: May 2007
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: clofarabine

    Cohort N Clofarabine (mg/m2/day)

    1. 3-6 30
    2. 3-6 40
    3. 3-6 50
    4. 3-6 60
    5. 6-10 70
Detailed Description:

All patients will receive the same doses of etoposide and cyclophosphamide. The dose of clofarabine will be escalated in successive cohorts of patients. Using a standard dose escalation design, successive cohorts of 3 patients will be treated with escalating doses of clofarabine (see Section 5.5 below). At the MTD (or highest dose-level if the MTD is not reached), the cohort will be expanded to 10 patients to better investigate correlative studies and give some preliminary idea of efficacy.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Documentation of disease. Patients must have one of the following disease types:

    • Diffuse large cell non-Hodgkin's lymphoma, mediastinal B-cell lymphoma, or peripheral T-cell lymphoma that is:

      • Primary refractory (achievement less than complete response)
      • Relapsed and refractory (achievement less than a partial response) to at least a single salvage therapy
    • Relapsed or primary refractory Follicular lymphoma (FL) with a high FL International Prognostic Index.
    • Large cell transformation of lymphoma from a more indolent lymphoma (e.g., follicular, marginal zone, etc.)
    • Mantle cell lymphoma that is:

      • Primary Refractory (achievement less than complete response)
      • Relapsed (regardless of chemosensitivity of relapsed disease)
  2. Patients who received prior autologous stem cell transplantation are not eligible.
  3. Patient age 18-70 years
  4. Performance status ECOG 0-1
  5. Required baseline laboratory values:

    • LVEF > 45% corrected
    • DLCO > 50% of predicted value (corrected for hemoglobin)
    • Serum creatinine ≤ 2.0 mg/dl or estimated creatinine clearance of ≥60 ml/min
    • Bilirubin < 1 x upper limit of normal value.
    • AST and ALT < 1 x upper limit of normal value.
  6. Signed written informed consent. Patient must be capable of understanding the investigational nature of the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Exclusion Criteria:

  1. No active infection. Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection.
  2. No HIV disease. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.
  3. Non-pregnant and non-nursing. Treatment under this protocol would expose a fetus to significant risks. Women of childbearing potential should have a negative pregnancy test prior to study entry. Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives (Norplant®), or double barrier method (diaphragm plus condom).
  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: NCT00477945

Locations
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Sherif Farag, MD, PhD Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier: NCT00477945     History of Changes
Other Study ID Numbers: 0704-29 IUCRO-0187
Study First Received: May 22, 2007
Last Updated: March 30, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Non Hodgkin's Lymphoma
High Risk or Refractory Non Hodgkin's Lymphoma
APBSCT
clofarabine

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Clofarabine
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 26, 2014