Trial Outcomes & Findings for Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma (NCT NCT00644189)
NCT ID: NCT00644189
Last Updated: 2023-03-15
Results Overview
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.
COMPLETED
PHASE1/PHASE2
50 participants
after at most 6 28-day cycles
2023-03-15
Participant Flow
Participant milestones
| Measure |
Clofarabine 1 mg
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.
|
Clofarabine 2 mg
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.
|
Clofarabine 4 mg
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.
|
Clofarabine: 3 mg
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.
|
|---|---|---|---|---|
|
Phase I
STARTED
|
3
|
3
|
6
|
18
|
|
Phase I
COMPLETED
|
3
|
3
|
6
|
18
|
|
Phase I
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Phase II
STARTED
|
0
|
0
|
0
|
50
|
|
Phase II
Completed All 6 Cycles of Treatment
|
0
|
0
|
0
|
19
|
|
Phase II
COMPLETED
|
0
|
0
|
0
|
50
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma
Baseline characteristics by cohort
| Measure |
Clofarabine Phase I
n=30 Participants
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.
|
|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
|
Number of prior regimens
|
1 number of prior regimens
n=5 Participants
|
|
Histologies
follicular lymphoma (FL)
|
7 Participants
n=5 Participants
|
|
Histologies
small lymphocytic lymphoma (SLL)
|
6 Participants
n=5 Participants
|
|
Histologies
diffuse large B-cell lymphoma (DLBCL)
|
3 Participants
n=5 Participants
|
|
Histologies
marginal zone lymphoma (MZL)
|
7 Participants
n=5 Participants
|
|
Histologies
mantle cell lymphoma (MCL)
|
6 Participants
n=5 Participants
|
|
Histologies
T-cell lymphoma (TCL)
|
0 Participants
n=5 Participants
|
|
Histologies
lymphoplasmacytic lymphoma (LPL)
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: after at most 6 28-day cyclesPopulation: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
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.
Outcome measures
| Measure |
Phase I-II
n=50 Participants
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.
|
|---|---|
|
All Phase I-II Participants: Overall Response Rate (ORR)
|
28 percentage of participants
Interval 16.0 to 42.0
|
PRIMARY outcome
Timeframe: after at most 6 28-day cyclesPopulation: Phase I participants only
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.
Outcome measures
| Measure |
Phase I-II
n=30 Participants
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.
|
|---|---|
|
Phase I Participants Only: Overall Response Rate (ORR)
|
47 percentage of participants
Interval 31.0 to 63.0
|
SECONDARY outcome
Timeframe: after at most 6 28-day cyclesPopulation: only participants from phase I-II trial who were treated at the RP2D (3mg)
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.
Outcome measures
| Measure |
Phase I-II
n=36 Participants
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.
|
|---|---|
|
Phase I-II Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
|
28 percentage of participants
Interval 14.0 to 45.0
|
SECONDARY outcome
Timeframe: at 1 and 2 yearsPopulation: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
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.
Outcome measures
| Measure |
Phase I-II
n=50 Participants
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.
|
|---|---|
|
All Phase I-II Participants: Progression-free Survival (PFS)
1-year PFS
|
32 percentage of patients
Interval 20.0 to 45.0
|
|
All Phase I-II Participants: Progression-free Survival (PFS)
2-year PFS
|
16 percentage of patients
Interval 7.5 to 27.0
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: all participants from phase I-II trial who are treated with any of the 4 dose levels of oral clofarabine
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)
Outcome measures
| Measure |
Phase I-II
n=50 Participants
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.
|
|---|---|
|
All Phase I-II Participants: Overall Survival (OS)
|
58 percentage of participants
Interval 43.0 to 71.0
|
SECONDARY outcome
Timeframe: during 6 28-day cycles and 90 days outPopulation: all phase I-II trial participants who are treated with any of the 4 dose levels of oral clofarabine
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)
Outcome measures
| Measure |
Phase I-II
n=50 Participants
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.
|
|---|---|
|
All Phase I-II Participants: Safety
Any grade 3-4 toxicity
|
29 Participants
|
|
All Phase I-II Participants: Safety
Leukopenia and neutropenia
|
24 Participants
|
|
All Phase I-II Participants: Safety
Thrombocytopenia
|
15 Participants
|
|
All Phase I-II Participants: Safety
Anemia
|
7 Participants
|
|
All Phase I-II Participants: Safety
Fatigue
|
3 Participants
|
SECONDARY outcome
Timeframe: after at most 6 28-day cyclesPopulation: Phase I participants only who were treated at the RP2D (3mg)
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.
Outcome measures
| Measure |
Phase I-II
n=16 Participants
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.
|
|---|---|
|
Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
Complete Response (CR)
|
5 Participants
|
|
Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
Partial Response (PR)
|
4 Participants
|
|
Phase I Participants Treated at the RP2D (3mg): Overall Response Rate (ORR)
Stable Disease (SD) or Progressive Disease (PD)
|
7 Participants
|
SECONDARY outcome
Timeframe: at 17 monthsPopulation: Phase I participants only
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.
Outcome measures
| Measure |
Phase I-II
n=30 Participants
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.
|
|---|---|
|
Phase I Participants: Progression-free Survival (PFS)
|
34 percentage of participants
Interval 17.0 to 51.0
|
SECONDARY outcome
Timeframe: at 17 monthsPopulation: Phase I participants only
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)
Outcome measures
| Measure |
Phase I-II
n=30 Participants
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.
|
|---|---|
|
All Phase I Participants: Overall Survival (OS)
|
75 percentage of participants
Interval 62.0 to 89.0
|
SECONDARY outcome
Timeframe: during 6 28-day cycles and 90 days outPopulation: Phase I participants only
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)
Outcome measures
| Measure |
Phase I-II
n=30 Participants
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.
|
|---|---|
|
Phase I Participants: Safety
Anemia
|
19 Participants
|
|
Phase I Participants: Safety
Neutropenia
|
18 Participants
|
|
Phase I Participants: Safety
Thrombocytopenia
|
9 Participants
|
|
Phase I Participants: Safety
Fatigue
|
8 Participants
|
|
Phase I Participants: Safety
Neutropenic fever
|
1 Participants
|
|
Phase I Participants: Safety
Grade 3-4 infections
|
3 Participants
|
|
Phase I Participants: Safety
Any grade 3-4 toxicity
|
20 Participants
|
Adverse Events
Clofarabine
Serious adverse events
| Measure |
Clofarabine
n=50 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
10.0%
5/50 • Number of events 6
|
|
Nervous system disorders
CNS Cerebrovascular Ischemia
|
2.0%
1/50 • Number of events 1
|
|
Nervous system disorders
CNS Hemorrhage
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Death (due to disease Progression)
|
4.0%
2/50 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
4.0%
2/50 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.0%
3/50 • Number of events 3
|
|
General disorders
Fatigue
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
4.0%
2/50 • Number of events 2
|
|
General disorders
Fever
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.0%
1/50 • Number of events 1
|
|
Vascular disorders
Hypotension
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Infection
|
4.0%
2/50 • Number of events 2
|
|
Renal and urinary disorders
Kidney Failure
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.0%
1/50 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.0%
3/50 • Number of events 5
|
|
General disorders
Pain - Left Flank
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Pericarditis
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Petechia
|
2.0%
1/50 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
suspected GI Bleed
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Suspected respiratory tract infection
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
10.0%
5/50 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Weakness in legs
|
2.0%
1/50 • Number of events 1
|
Other adverse events
| Measure |
Clofarabine
n=50 participants at risk
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.
|
|---|---|
|
General disorders
Chills
|
100.0%
50/50 • Number of events 255
|
|
Gastrointestinal disorders
Ascites
|
100.0%
50/50 • Number of events 254
|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
50/50 • Number of events 253
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
100.0%
50/50 • Number of events 253
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
100.0%
50/50 • Number of events 253
|
|
Gastrointestinal disorders
Nausea
|
100.0%
50/50 • Number of events 252
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
50/50 • Number of events 252
|
|
Blood and lymphatic system disorders
Leukocytosis
|
100.0%
50/50 • Number of events 252
|
|
General disorders
Head/headache
|
100.0%
50/50 • Number of events 252
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
100.0%
50/50 • Number of events 244
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
24.0%
12/50 • Number of events 27
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial stricture
|
22.0%
11/50 • Number of events 24
|
|
Nervous system disorders
Brachial plexopathy
|
22.0%
11/50 • Number of events 16
|
|
Gastrointestinal disorders
Constipation
|
22.0%
11/50 • Number of events 15
|
|
Metabolism and nutrition disorders
Hypokalemia
|
20.0%
10/50 • Number of events 32
|
|
Metabolism and nutrition disorders
AST, SGOT
|
20.0%
10/50 • Number of events 17
|
|
Metabolism and nutrition disorders
Dehydration
|
16.0%
8/50 • Number of events 14
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
16.0%
8/50 • Number of events 14
|
|
Nervous system disorders
Movements involuntary
|
14.0%
7/50 • Number of events 17
|
|
General disorders
Back, pain
|
14.0%
7/50 • Number of events 12
|
|
General disorders
Joint, pain
|
14.0%
7/50 • Number of events 10
|
|
General disorders
Abdomen, pain
|
14.0%
7/50 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Chemoradiation dermatitis
|
14.0%
7/50 • Number of events 7
|
|
Gastrointestinal disorders
Dyspepsia
|
12.0%
6/50 • Number of events 9
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
10.0%
5/50 • Number of events 16
|
|
Blood and lymphatic system disorders
Edema limb
|
10.0%
5/50 • Number of events 14
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
10.0%
5/50 • Number of events 11
|
|
Immune system disorders
Allergic rhinitis
|
10.0%
5/50 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
10.0%
5/50 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypernatremia
|
10.0%
5/50 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyponatremia
|
10.0%
5/50 • Number of events 6
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.0%
4/50 • Number of events 13
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
8.0%
4/50 • Number of events 9
|
|
General disorders
Insomnia
|
8.0%
4/50 • Number of events 8
|
|
Gastrointestinal disorders
Anorexia
|
8.0%
4/50 • Number of events 7
|
|
Infections and infestations
Infection Gr0-2 neut, upper airway
|
8.0%
4/50 • Number of events 7
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
6.0%
3/50 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory-other
|
8.0%
4/50 • Number of events 6
|
|
General disorders
Fatigue
|
8.0%
4/50 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
6.0%
3/50 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
6.0%
3/50 • Number of events 7
|
|
General disorders
Pelvic, pain
|
6.0%
3/50 • Number of events 6
|
|
Infections and infestations
Infection Gr0-2 neut, skin
|
6.0%
3/50 • Number of events 5
|
|
Cardiac disorders
Cardiac-other
|
6.0%
3/50 • Number of events 4
|
|
General disorders
Fever w/o neutropenia
|
6.0%
3/50 • Number of events 4
|
|
General disorders
Weight loss
|
6.0%
3/50 • Number of events 3
|
|
General disorders
Pain-other
|
6.0%
3/50 • Number of events 3
|
Additional Information
Jeremy Abramson, MD
Massachusetts General Hospital Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place