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Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

This study has been terminated.
(discontinuation of the drug formulation used in the study)
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Jeremy Abramson, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00644189
First received: March 24, 2008
Last updated: March 26, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
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 Drug: Clofarabine Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Oral Clofarabine in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Jeremy Abramson, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • All Phase I-II Participants: Overall Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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:
  • Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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)

  • All Phase I-II Participants: Safety [ Time Frame: 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) [ Time Frame: 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.


  • Phase I Participants: Progression-free Survival (PFS) [ Time Frame: 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.


  • All Phase I Participants: Overall Survival (OS) [ Time Frame: 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 Participants: Safety [ Time Frame: 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)


Enrollment: 50
Study Start Date: June 2008
Study Completion Date: December 2016
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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.
Other Name: Clolar

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00644189

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Jeremy Abramson, MD Massachusetts General Hospital
  More Information

Responsible Party: Jeremy Abramson, MD, Director, Lymphoma Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00644189     History of Changes
Other Study ID Numbers: 07-401
Study First Received: March 24, 2008
Results First Received: February 2, 2017
Last Updated: March 26, 2017

Keywords provided by Jeremy Abramson, MD, Massachusetts General Hospital:
clofarabine
Clolar
lymphoma
NHL
oral chemotherapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on August 23, 2017