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Clofarabine in Treating Patients With T-Cell or Natural Killer-Cell Non-Hodgkin's Lymphoma That Has Relapsed or Not Responded to Previous Treatment

A Phase I/II Study of Clofarabine in Patients With Relapsed T-Cell and NK-Cell Lymphomas

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00416351
Enrollment
29
Registered
2006-12-28
Start date
2006-06-27
Completion date
2021-03-01
Last updated
2022-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia, Lymphoma, Small Intestine Cancer

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

DRUGclofarabine

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
University of Rochester
CollaboratorOTHER
The Cleveland Clinic
CollaboratorOTHER
Memorial Sloan Kettering Cancer Center
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
2 Years to 120 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Maximum Tolerated Dose2 years
Response Rate for Participants With Non-Hodgkin's Lymphoma2 yearsResponse 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

MeasureTime frameDescription
Participants Evaluated for Toxicity2 yearsToxicity as defined by NCI Common Terminology Criteria for Adverse Events v 3.0

Countries

United States

Participant flow

Participants by arm

ArmCount
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
Total29

Baseline characteristics

Characteristic4 mg/m2/Day ClofarabineTotal28 mg/m2/Day Clofarabine20 mg/m2/Day Clofarabine13.2 mg/m2/Day Clofarabine8 mg/m2/Day Clofarabine
Age, Continuous62 years59 years54.5 years54.1 years58 years65.3 years
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants28 Participants4 Participants17 Participants4 Participants2 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants2 Participants0 Participants1 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants7 Participants2 Participants5 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants2 Participants0 Participants1 Participants1 Participants0 Participants
Race (NIH/OMB)
White
0 Participants18 Participants2 Participants10 Participants3 Participants3 Participants
Region of Enrollment
United States
1 Participants29 Participants4 Participants17 Participants4 Participants3 Participants
Sex: Female, Male
Female
1 Participants14 Participants0 Participants9 Participants2 Participants2 Participants
Sex: Female, Male
Male
0 Participants15 Participants4 Participants8 Participants2 Participants1 Participants

Adverse events

Event typeEG000
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 / 13 / 33 / 412 / 174 / 4
other
Total, other adverse events
1 / 13 / 34 / 417 / 174 / 4
serious
Total, serious adverse events
0 / 11 / 31 / 413 / 174 / 4

Outcome results

Primary

Maximum Tolerated Dose

Time frame: 2 years

ArmMeasureValue (NUMBER)
ClofarabineMaximum Tolerated Dose20 mg/m2 of clofarabine
Primary

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

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaPartial Response (PR)0 Participants
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaNot Evaluable0 Participants
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaComplete Response0 Participants
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease (SD)0 Participants
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaProgression of Disease (POD)1 Participants
ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease/Progression of Disease (SD/POD)0 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease (SD)1 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease/Progression of Disease (SD/POD)0 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaNot Evaluable0 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaPartial Response (PR)0 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaComplete Response1 Participants
8 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaProgression of Disease (POD)1 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaPartial Response (PR)0 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease (SD)0 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaComplete Response1 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaProgression of Disease (POD)2 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease/Progression of Disease (SD/POD)1 Participants
13.2 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaNot Evaluable0 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaPartial Response (PR)1 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaProgression of Disease (POD)11 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease (SD)2 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaComplete Response1 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease/Progression of Disease (SD/POD)2 Participants
20 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaNot Evaluable0 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease/Progression of Disease (SD/POD)0 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaComplete Response0 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaPartial Response (PR)0 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaStable Disease (SD)1 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaProgression of Disease (POD)3 Participants
28 mg/m2/Day ClofarabineResponse Rate for Participants With Non-Hodgkin's LymphomaNot Evaluable0 Participants
Secondary

Participants Evaluated for Toxicity

Toxicity as defined by NCI Common Terminology Criteria for Adverse Events v 3.0

Time frame: 2 years

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ClofarabineParticipants Evaluated for Toxicity1 Participants
8 mg/m2/Day ClofarabineParticipants Evaluated for Toxicity3 Participants
13.2 mg/m2/Day ClofarabineParticipants Evaluated for Toxicity4 Participants
20 mg/m2/Day ClofarabineParticipants Evaluated for Toxicity17 Participants
28 mg/m2/Day ClofarabineParticipants Evaluated for Toxicity4 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026