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Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

Primary Purpose

Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Clofarabine
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring clofarabine, Clolar, lymphoma, NHL, oral chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Clofarabine

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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)
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)
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.
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.
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)
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)

Full Information

First Posted
March 24, 2008
Last Updated
March 13, 2023
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00644189
Brief Title
Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma
Official Title
A Phase II Study of Oral Clofarabine in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
July 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Genzyme, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
clofarabine, Clolar, lymphoma, NHL, oral chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clofarabine
Arm Type
Other
Arm Description
Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clolar
Intervention Description
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 Measure Information:
Title
All Phase I-II Participants: Overall Response Rate (ORR)
Description
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.
Time Frame
after at most 6 28-day cycles
Title
Phase I Participants Only: Overall Response Rate (ORR)
Description
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.
Time Frame
after at most 6 28-day cycles
Secondary Outcome Measure Information:
Title
Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
Description
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.
Time Frame
after at most 6 28-day cycles
Title
All Phase I-II Participants: Progression-free Survival (PFS)
Description
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.
Time Frame
at 1 and 2 years
Title
All Phase I-II Participants: Overall Survival (OS)
Description
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)
Time Frame
3 years
Title
All Phase I-II Participants: Safety
Description
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)
Time Frame
during 6 28-day cycles and 90 days out
Title
Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
Description
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.
Time Frame
after at most 6 28-day cycles
Title
Phase I Participants: Progression-free Survival (PFS)
Description
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.
Time Frame
at 17 months
Title
All Phase I Participants: Overall Survival (OS)
Description
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)
Time Frame
at 17 months
Title
Phase I Participants: Safety
Description
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)
Time Frame
during 6 28-day cycles and 90 days out

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Abramson, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

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