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

Sponsor

Indiana University School of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00477945

Collaborator

Genzyme, a Sanofi Company (Industry)

Enrollment

Location

42.1

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Non Hodgkin's Lymphoma	Drug: clofarabine	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Nov 1, 2010

Actual Study Completion Date :

Nov 1, 2010

Outcome Measures

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. [1 yr]

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 [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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)

Patients who received prior autologous stem cell transplantation are not eligible.
Patient age 18-70 years
Performance status ECOG 0-1
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.

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:

No active infection. Patients with active infections requiring oral or intravenous antibiotics are not eligible for enrollment until resolution of infection.
No HIV disease. Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.
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).