Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

Phase 1

Completed

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

• Registration Number: NCT00644189
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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

* 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.

Study Timeline

• Study First Submitted: 2008-03-24
• Study First Submitted QC: 2008-03-24
• Study First Posted: 2008-03-26
• Study Start: 2008-06
• Primary Completion: 2013-12
• Results First Submitted: 2017-02-02
• Results First Submitted QC: 2017-03-26
• Results First Posted: 2017-05-08
• Study Completion: 2021-07
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-13
• Last Update Posted: 2023-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Clofarabine	Clofarabine	Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles.

Primary Outcome Measures

Name	Time	Method
All Phase I-II Participants: Overall Response Rate (ORR)	after at most 6 28-day cycles	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.
Phase I Participants Only: Overall Response Rate (ORR)	after at most 6 28-day cycles	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.

Secondary Outcome Measures

Name	Time	Method
All Phase I Participants: Overall Survival (OS)	at 17 months	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)
Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)	after at most 6 28-day cycles	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.
All Phase I-II Participants: Progression-free Survival (PFS)	at 1 and 2 years	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.
All Phase I-II Participants: Overall Survival (OS)	3 years	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)
Phase I Participants: Progression-free Survival (PFS)	at 17 months	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.
Phase I Participants: Safety	during 6 28-day cycles and 90 days out	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)
All Phase I-II Participants: Safety	during 6 28-day cycles and 90 days out	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)
Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)	after at most 6 28-day cycles	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.

Trial Locations

Locations (2)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States