Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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Oral clofarabine is related to two intravenous chemotherapy drugs used for this disease and works in two different ways. It affects the development of new cancer cells by blocking two enzymes that cancer cells need to reproduce. When these enzymes are blocked, the cancer call can no longer prepare the DNA needed to make new cells. Clofarabine also encourages existing cancer cells to die by disturbing components within the cancer cell. This causes the release of a substance that is fatal to the cell. This trial studies the efficacy of oral clofarabine in the treatment of relapsed non-Hodgkin lymphomas.

Detailed Description
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Each treatment cycle lasts four weeks during which time the participant will be taking study drug for the first three weeks only. Participants will be supplied with a study medication-dosing calendar for each treatment cycle. Clofarabine is a tablet that will be taken orally in the morning once daily on days 1 through 21 of each 28-day cycle. Participants can receive up to a total of 6 cycles if they do not experience any unacceptable side effects and if their cancer does not get worse. The following tests and procedures will be performed at specified intervals through out the treatment period: blood tests, physical examinations, vital signs, radiological exams and urine tests.

Official Title
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A Phase II Study of Oral Clofarabine in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma

Conditions
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Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, Low Grade B-cell Lymphoma, Not Otherwise Specified, Diffuse Large B-cell Lymphoma, Peripheral T-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Anaplastic Large-cell Lymphoma

Intervention / Treatment
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* Drug: Clofarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed relapsed or refractory NHL that includes: follicular lymphoma of any grade; marginal zone lymphoma; small lymphocytic lymphoma/chronic lymphocytic leukemia; mantle cell lymphoma; lymphoplasmacytic lymphoma; low-grade B-cell lymphoma not otherwise specified; diffuse large B-cell lymphoma, anaplastic large cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma. One or more prior line of chemotherapy, immunotherapy, or radioimmunotherapy. Measurable disease on cross sectional imaging of at least 2cm. ECOG Performance Status 0-2 18 years of age or older Life expectancy of greater than 3 months Normal organ and marrow function as outlined in the protocol Must agree to use adequate contraception prior to study entry and for the duration of study participation Exclusion Criteria: Patients who have had chemotherapy, rituximab, or radiotherapy within 4 weeks, or radioimmunotherapy within 8 weeks prior to entering the study Receiving any other investigational agent Known brain metastases History of allergic reactions attributed to compounds of similar chemical or biologic composition to Clofarabine Systemic fungal, bacterial, viral, or other infection not controlled Pregnant or lactating Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for over one year Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Prior allogeneic stem cell transplantation

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Clofarabine<br>Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles. | Drug: Clofarabine<br>* Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles.<br>* Other names: Clolar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Phase I-II Participants: Overall Response Rate (ORR) | Determine the efficacy of oral clofarabine (any of the 4 dose levels: 1mg, 2mg, 4mg, and 3mg) in all phase I-II trial patients with relapsed/refractory non-Hodgkin lymphomas. 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. | after at most 6 28-day cycles | 
| Phase I Participants Only: Overall Response Rate (ORR) | Determine the efficacy of oral clofarabine (any of the 4 dose levels: 1mg, 2mg, 4mg, and 3mg) in all phase I trial patients with relapsed/refractory non-Hodgkin lymphomas. 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. | after at most 6 28-day cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | To determine the efficacy of oral clofarabine (3mg) in patients with relapsed/refractory non-Hodgkin lymphoma. The 3mg dose was declared the recommended phase 2 dose (RP2D) from phase I. 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. | after at most 6 28-day cycles | 
| All Phase I-II Participants: Progression-free Survival (PFS) | Determine the progression-free survival rate among all phase I-II trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | at 1 and 2 years | 
| All Phase I-II Participants: Overall Survival (OS) | Determine the overall survival rate among all phase I-II trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg) | 3 years | 
| All Phase I-II Participants: Safety | Grade 3-4 toxicities among all phase I-II trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg) | during 6 28-day cycles and 90 days out | 
| Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | To determine the efficacy of oral clofarabine (3mg) in patients with relapsed/refractory non-Hodgkin lymphoma. The 3mg dose was declared the recommended phase 2 dose (RP2D) from phase I. 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. | after at most 6 28-day cycles | 
| Phase I Participants: Progression-free Survival (PFS) | Determine the progression-free survival rate among all phase I trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | at 17 months | 
| All Phase I Participants: Overall Survival (OS) | Determine the overall survival rate among all phase I trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg) | at 17 months | 
| Phase I Participants: Safety | Grade 2-4 toxicities and grade 3-4 infections among all phase I trial participants who are treated with any of the 4 dose levels of oral clofarabine (1mg, 2mg, 4mg, or 3mg) | during 6 28-day cycles and 90 days out | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clofarabine, Clolar, lymphoma, NHL, oral chemotherapy