Anaplastic Large-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Diffuse Large B-cell Lymphoma, Follicular Lymphoma, Low Grade B-cell Lymphoma, Not Otherwise Specified, Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Peripheral T-cell Lymphoma, Small Lymphocytic Lymphoma
Conditions
Keywords
clofarabine, Clolar, lymphoma, NHL, oral chemotherapy
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.
Interventions
DRUGClofarabine
Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles.
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Genzyme, a Sanofi Company
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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. |
| 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 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 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) |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine Phase I Taken orally once a day (in the AM) on days 1 through 21 of a 28-day cycle for a maximum of 6 cycles.
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. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Clofarabine Phase I |
|---|---|
| Age, Continuous | 62 years |
| Histologies diffuse large B-cell lymphoma (DLBCL) | 3 Participants |
| Histologies follicular lymphoma (FL) | 7 Participants |
| Histologies lymphoplasmacytic lymphoma (LPL) | 1 Participants |
| Histologies mantle cell lymphoma (MCL) | 6 Participants |
| Histologies marginal zone lymphoma (MZL) | 7 Participants |
| Histologies small lymphocytic lymphoma (SLL) | 6 Participants |
| Histologies T-cell lymphoma (TCL) | 0 Participants |
| Number of prior regimens | 1 number of prior regimens |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 50 |
| serious Total, serious adverse events | 15 / 50 |
Outcome results
Primary
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.
Time frame: after at most 6 28-day cycles
Population: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I-II | All Phase I-II Participants: Overall Response Rate (ORR) | 28 percentage of participants |
Primary
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.
Time frame: after at most 6 28-day cycles
Population: Phase I participants only
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase I-II | Phase I Participants Only: Overall Response Rate (ORR) | 47 percentage of participants |
Secondary
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)
Time frame: 3 years
Population: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I-II | All Phase I-II Participants: Overall Survival (OS) | 58 percentage of participants |
Secondary
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.
Time frame: at 1 and 2 years
Population: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I-II | All Phase I-II Participants: Progression-free Survival (PFS) | 1-year PFS | 32 percentage of patients |
| Phase I-II | All Phase I-II Participants: Progression-free Survival (PFS) | 2-year PFS | 16 percentage of patients |
Secondary
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)
Time frame: during 6 28-day cycles and 90 days out
Population: all phase I-II trial participants who are treated with any of the 4 dose levels of oral clofarabine
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I-II | All Phase I-II Participants: Safety | Any grade 3-4 toxicity | 29 Participants |
| Phase I-II | All Phase I-II Participants: Safety | Leukopenia and neutropenia | 24 Participants |
| Phase I-II | All Phase I-II Participants: Safety | Thrombocytopenia | 15 Participants |
| Phase I-II | All Phase I-II Participants: Safety | Anemia | 7 Participants |
| Phase I-II | All Phase I-II Participants: Safety | Fatigue | 3 Participants |
Secondary
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)
Time frame: at 17 months
Population: Phase I participants only
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase I-II | All Phase I Participants: Overall Survival (OS) | 75 percentage of participants |
Secondary
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.
Time frame: after at most 6 28-day cycles
Population: only participants from phase I-II trial who were treated at the RP2D (3mg)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I-II | Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | 28 percentage of participants |
Secondary
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.
Time frame: at 17 months
Population: Phase I participants only
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase I-II | Phase I Participants: Progression-free Survival (PFS) | 34 percentage of participants |
Secondary
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)
Time frame: during 6 28-day cycles and 90 days out
Population: Phase I participants only
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I-II | Phase I Participants: Safety | Anemia | 19 Participants |
| Phase I-II | Phase I Participants: Safety | Neutropenia | 18 Participants |
| Phase I-II | Phase I Participants: Safety | Thrombocytopenia | 9 Participants |
| Phase I-II | Phase I Participants: Safety | Fatigue | 8 Participants |
| Phase I-II | Phase I Participants: Safety | Neutropenic fever | 1 Participants |
| Phase I-II | Phase I Participants: Safety | Grade 3-4 infections | 3 Participants |
| Phase I-II | Phase I Participants: Safety | Any grade 3-4 toxicity | 20 Participants |
Secondary
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.
Time frame: after at most 6 28-day cycles
Population: Phase I participants only who were treated at the RP2D (3mg)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase I-II | Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | Complete Response (CR) | 5 Participants |
| Phase I-II | Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | Partial Response (PR) | 4 Participants |
| Phase I-II | Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR) | Stable Disease (SD) or Progressive Disease (PD) | 7 Participants |