Leukemia, Lymphoma, Small Intestine Cancer
Conditions
Keywords
anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult T-cell leukemia/lymphoma, recurrent mycosis fungoides/Sezary syndrome, adult nasal type extranodal NK/T-cell lymphoma, prolymphocytic leukemia, childhood nasal type extranodal NK/T-cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works in treating patients with T-cell or natural killer-cell lymphoma that has relapsed or not responded to previous treatment.
Detailed description
OBJECTIVES: Primary * Determine the maximum tolerated dose of clofarabine in patients with relapsed or refractory T-cell or natural killer-cell lymphoma. * Determine the toxicity of this drug in these patients. * Determine, preliminarily, the efficacy of this drug, in terms of response rate, in these patients. OUTLINE: This is a phase I, non-randomized, dose-escalation study followed by an open-label, phase II study. * Phase I: Patients receive clofarabine IV over 1 hour once daily on days 1-3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) or complete response (CR) may receive 2 additional courses of treatment. Patients with PR or CR after completing 4 courses of therapy may receive 2 additional courses. Cohorts of 1-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive clofarabine as in phase I at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months for 2 years.
Interventions
Sponsors
Study design
Eligibility
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed T-cell or natural killer (NK)-cell lymphoma, including any of the following subtypes: * Blastic NK-cell lymphoma * T/NK-cell lymphoma/leukemia * Adult T-cell lymphoma/leukemia * T-cell prolymphocytic leukemia * T-lymphoblastic lymphoma * Peripheral T-cell lymphoma, not otherwise specified * Angioimmunoblastic T-cell lymphoma * Anaplastic large cell lymphoma * Transformed mycosis fungoides * Subcutaneous panniculitis-like T-cell lymphoma * Nasal T/NK-cell lymphoma * Enteropathy-type T-cell lymphoma * Hepatosplenic gamma/delta T-cell lymphoma * Relapsed or refractory disease, meeting both of the following criteria: * Must have been treated with prior cytotoxic chemotherapy and/or monoclonal antibody therapy * No standard curative treatment exists * Allogeneic bone marrow transplantation is not considered standard curative treatment * Evaluable disease (Phase I) * Measurable disease, defined as any nodal site or mass lesion ≥ 1.5 cm in longest transverse diameter on physical exam or CT scan OR a measurable extranodal site \> 1 cm (Phase II) * Patients with evaluable blood- or marrow-based disease are eligible PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/mm³ (Phase I) * Absolute neutrophil count ≥ 500/mm³ (Phase II) * Platelet count ≥ 100,000/mm³ (Phase I) * Platelet count ≥ 50,000/mm³ (Phase II) * Creatinine \< 2.0 mg/dL\* * Bilirubin ≤ 2.0 times upper limit of normal (ULN)\* * AST and ALT ≤ 2.5 times ULN\* * No active infection requiring antibiotics * No New York Heart Association class III or IV congestive heart failure * No known HIV positivity * No other active malignancy requiring therapy * No other serious or life-threatening condition deemed unacceptable by the principal investigator * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception NOTE: \*Unless due to lymphoma and patients are entering to the phase II portion of the study PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 3 weeks since prior therapy, including any of the following: * Interferon * Antibody therapy * Retinoids * Other non-chemotherapeutic treatment * Concurrent stable-dose corticosteroids allowed * No colony-stimulating factor therapy during the first course of study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose | 2 years | — |
| Response Rate for Participants With Non-Hodgkin's Lymphoma | 2 years | Response rate as defined by complete remission, complete remission unconfirmed, partial remission, positron emission tomography (PET)-negative partial remission, stable disease, and progressive disease (Phase II) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Evaluated for Toxicity | 2 years | Toxicity as defined by NCI Common Terminology Criteria for Adverse Events v 3.0 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 4 mg/m2/Day Clofarabine Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | 1 |
| 8 mg/m2/Day Clofarabine Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | 3 |
| 13.2 mg/m2/Day Clofarabine Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | 4 |
| 20 mg/m2/Day Clofarabine Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | 17 |
| 28 mg/m2/Day Clofarabine Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | 4 |
| Total | 29 |
Baseline characteristics
| Characteristic | 4 mg/m2/Day Clofarabine | Total | 28 mg/m2/Day Clofarabine | 20 mg/m2/Day Clofarabine | 13.2 mg/m2/Day Clofarabine | 8 mg/m2/Day Clofarabine |
|---|---|---|---|---|---|---|
| Age, Continuous | 62 years | 59 years | 54.5 years | 54.1 years | 58 years | 65.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 28 Participants | 4 Participants | 17 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 7 Participants | 2 Participants | 5 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 18 Participants | 2 Participants | 10 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 1 Participants | 29 Participants | 4 Participants | 17 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 14 Participants | 0 Participants | 9 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 15 Participants | 4 Participants | 8 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 3 / 3 | 3 / 4 | 12 / 17 | 4 / 4 |
| other Total, other adverse events | 1 / 1 | 3 / 3 | 4 / 4 | 17 / 17 | 4 / 4 |
| serious Total, serious adverse events | 0 / 1 | 1 / 3 | 1 / 4 | 13 / 17 | 4 / 4 |
Outcome results
Maximum Tolerated Dose
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine | Maximum Tolerated Dose | 20 mg/m2 of clofarabine |
Response Rate for Participants With Non-Hodgkin's Lymphoma
Response rate as defined by complete remission, complete remission unconfirmed, partial remission, positron emission tomography (PET)-negative partial remission, stable disease, and progressive disease (Phase II)
Time frame: 2 years
Population: Evaluable participants with Non-Hodgkin's Lymphoma
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Partial Response (PR) | 0 Participants |
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Not Evaluable | 0 Participants |
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Complete Response | 0 Participants |
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease (SD) | 0 Participants |
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Progression of Disease (POD) | 1 Participants |
| Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease/Progression of Disease (SD/POD) | 0 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease (SD) | 1 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease/Progression of Disease (SD/POD) | 0 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Not Evaluable | 0 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Partial Response (PR) | 0 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Complete Response | 1 Participants |
| 8 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Progression of Disease (POD) | 1 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Partial Response (PR) | 0 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease (SD) | 0 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Complete Response | 1 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Progression of Disease (POD) | 2 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease/Progression of Disease (SD/POD) | 1 Participants |
| 13.2 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Not Evaluable | 0 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Partial Response (PR) | 1 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Progression of Disease (POD) | 11 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease (SD) | 2 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Complete Response | 1 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease/Progression of Disease (SD/POD) | 2 Participants |
| 20 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Not Evaluable | 0 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease/Progression of Disease (SD/POD) | 0 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Complete Response | 0 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Partial Response (PR) | 0 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Stable Disease (SD) | 1 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Progression of Disease (POD) | 3 Participants |
| 28 mg/m2/Day Clofarabine | Response Rate for Participants With Non-Hodgkin's Lymphoma | Not Evaluable | 0 Participants |
Participants Evaluated for Toxicity
Toxicity as defined by NCI Common Terminology Criteria for Adverse Events v 3.0
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Clofarabine | Participants Evaluated for Toxicity | 1 Participants |
| 8 mg/m2/Day Clofarabine | Participants Evaluated for Toxicity | 3 Participants |
| 13.2 mg/m2/Day Clofarabine | Participants Evaluated for Toxicity | 4 Participants |
| 20 mg/m2/Day Clofarabine | Participants Evaluated for Toxicity | 17 Participants |
| 28 mg/m2/Day Clofarabine | Participants Evaluated for Toxicity | 4 Participants |