Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma

Study Overview
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Brief Summary
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Clofarabine is a new chemotherapy drug which was FDA approved for the treatment of acute lymphocytic leukemia in children. This study is being done to see if Clofarabine works in adult patients with B-cell types of lymphoma. This research is being done to develop new treatments for patients with lymphoma whose cancer has returned or resisted treatment with previous chemotherapy.

Official Title
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Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermed.Grade B-Cell/T-Cell Lymphoma

Conditions
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B-Cell Lymphoma

Intervention / Treatment
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* Drug: Clofarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients who are at least 18 years old Histologically confirmed low grade or intermediate-grade B-cell lymphoma Relapsed or refractory to at least one standard chemotherapy regimen. Patients who have received Rituximab alone without having received a cytotoxic agent are not eligible. Measurable disease, defined by the Cheson lymphoma criteria. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy greater than 12 weeks Laboratory values obtained ≤2 weeks prior to entry Absolute neutrophil count (ANC) ≥ 1000 x 10 9/L White blood cell (WBC) count > 2.5 x 10 9/L Platelets ≥ 75 x 10 9/L Hemoglobin (Hg) > 9.0 g/dL Total bilirubin ≤2.0 mg/dL Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3 × upper limit of normal (ULN) Serum creatinine ≤2.0 mg/dL Normal cardiac function, defined as an ejection fraction ≥45% determined by pretreatment radionuclide ventriculography (RVG) or echocardiogram. 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 minimum of 6 months after study treatment. Exclusion Criteria: Previously untreated B-cell lymphoma. Received previous treatment with clofarabine. Patients with known AIDS-related or HIV-positive lymphoma. Autologous bone marrow or stem cell transplant within 6 months of study entry. Prior radiotherapy to the only site of measurable disease. Any medical condition that requires chronic use of oral high-dose corticosteroids greater than 20 mg/day prednisone. Active autoimmune thrombocytopenia. Use of 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 on parenteral antifungal therapy). 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 system (CNS) lymphoma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Clofarabine<br>* The starting dose of clofarabine will be 10 mg/m2 once a week for 3 weeks repeated every 4 weeks with dose escalations to 15, 20 , 30 and 40 mg/m2/week.<br>* Other names: Cl-F-ara-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tolerated dose (MTD) of clofarabine |  | at the completion of dose escalation | 
| characterize and quantify the toxicity profile associated with clofarabine |  | upon completion of the study | 
| determine the overall response rate, plus partial response of clofarabine |  | upon completion of the study |