Anaplastic Large Cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma
Conditions
Brief summary
This phase II trial is studying how well ixabepilone works in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop cancer cells from dividing so they stop growing or die.
Detailed description
OBJECTIVES: I. Determine the objective overall response rate of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma treated with BMS-247550 (ixabepilone). II. Determine the safety and toxicity of this drug in these patients. III. Determine the duration of response, overall survival, and time to progression in patients treated with this drug. OUTLINE: This is a multi-center study. Patients receive ixabepilone intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or if the patient becomes a candidate for stem cell transplantation. Patients are followed every 8 weeks until disease progression.
Interventions
DRUGixabepilone
Given IV
Sponsors
National Cancer Institute (NCI)
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 aggressive non-Hodgkin's lymphoma of 1 of the following cellular types: * Grade III follicular center * Diffuse large B-cell * Mantle cell * Primary mediastinal B-cell * Burkitt's * High-grade B-cell (Burkitt-like) * Anaplastic large cell of 1 of the following subtypes: * CD30-positive * T-cell * Null cell * Hodgkin's-like * Relapsed or refractory disease after prior standard chemotherapy, meeting criteria for 1of the following cohorts: * Cohort 1 (relapsed but chemosensitive): Prior complete response (CR) or partial response (PR) lasting at least 4 weeks after the most recent prior therapy * Cohort 2 (refractory): Stable disease or less than a PR after the most recent prior therapy * No progressive disease after the most recent prior therapy * Measurable disease * At least 1 bidimensionally measurable lesion at least 10 mm by conventional techniques or clinical exam * Ineligible for or unwilling to undergo hematopoietic stem cell transplantation * Patients requiring debulking prior to transplant allowed * No known CNS involvement by lymphoma * Prior CNS disease that has been successfully treated in patients with relapsed disease exclusively outside of the CNS may be allowed by the principal investigator * Performance status - ECOG 0-2 * More than 3 months * WBC at least 3,000/mm\^3 * Absolute neutrophil count at least 1,200/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than 1.5 mg/dL * AST/ALT no greater than 2.5 times upper limit of normal * Creatinine no greater than 1.5 mg/dL * Creatinine clearance at least 60 mL/min * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior allergic reaction or hypersensitivity to compounds containing Cremophor EL or agents of similar chemical or biological composition to BMS-247550 * No peripheral neuropathy grade 2 or greater * No other currently active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix (previously treated malignancy allowed if considered to be at less than 30% risk of relapse) * No ongoing or active infection * No psychiatric illness or social situation that would preclude study compliance * No other concurrent uncontrolled illness * No colony-stimulating factors (CSFs) within 24 hours of study chemotherapy * No CSFs during first course of study therapy * No concurrent filgrastim-SD/01 * No concurrent immunotherapy * See Disease Characteristics * At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) * No other concurrent chemotherapy * No concurrent hormonal therapy * At least 4 weeks since prior radiotherapy * No concurrent therapeutic radiotherapy * At least 4 weeks since prior surgery * Recovered from prior therapy * At least 7 days since prior cimetidine * No concurrent cimetidine * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No other concurrent anticancer medications * No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Overall Response Rate | up to 3 years | The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10561185) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires \>=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR. |
| Safety and Toxicity of Ixabepilone | up to 3 years | Number of patients experiencing adverse event grade 3 or above. Grade was determined by the National Cancer Institute Common Toxicity Criteria (CTC) version 2.0. Adverse events possibly, probably, or definitely attributed to use of ixabepilone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | up to 3 years | Duration of response was measured from the time measurement criteria are met for CR(complete response)/CRu(unconfirmed complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the 1999 international response criteria as published by Cheson, CR/CRu is defined as the disappearance of all target lesions; PR is defined as \>=50% decrease in the sum of the products of the greatest diameters; PD is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy. |
| Overall Survival | up to 3 years | Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive. |
| Time to Progression | up to 3 years | Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy. |
Countries
United States
Participant flow
Pre-assignment details
One patient never received treatment and was excluded from analysis.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Chemosensitive) Ixabepilone was administered intravenously at a dose of 20 mg/m\^2 over 1 hour weekly on days 1,8, and 15 of a 28-day cycle. Cohort 1(Chemosensitive) enrolled patients with a complete response or partial response lasting at least 4 weeks to their most recent therapy. | 39 |
| Cohort 2 (Chmoresistant) Ixabepilone was administered intravenously at a dose of 20 mg/m\^2 over 1 hour weekly on days 1,8, and 15 of a 28-day cycle. Cohort 2(Chemoresistant) enrolled patients with stable disease but less than a partial response to their most recent therapy. | 12 |
| Total | 51 |
Baseline characteristics
| Characteristic | Cohort 1 (Chemosensitive) | Cohort 2 (Chmoresistant) | Total |
|---|---|---|---|
| Age, Continuous | 64 years | 73 years | 66 years |
| LDH elevation No | 23 Participants | 6 Participants | 29 Participants |
| LDH elevation Yes | 16 Participants | 6 Participants | 22 Participants |
| Prior rituximab No | 5 Participants | 1 Participants | 6 Participants |
| Prior rituximab Yes | 34 Participants | 11 Participants | 45 Participants |
| Prior therapies 1 | 10 Participants | 4 Participants | 14 Participants |
| Prior therapies 2-3 | 17 Participants | 5 Participants | 22 Participants |
| Prior therapies 4 or more | 12 Participants | 3 Participants | 15 Participants |
| Race/Ethnicity, Customized African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 34 Participants | 12 Participants | 46 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 17 Participants |
| Sex: Female, Male Male | 27 Participants | 7 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 48 / 51 |
| serious Total, serious adverse events | 11 / 51 |
Outcome results
Primary
Objective Overall Response Rate
The 1999 international response criteria (http://www.ncbi.nlm.nih.gov/pubmed/10561185) as published by Cheson was used for the definition of target lesions and CT scans were used for response assessment. CR(complete response)/CRu(unconfirmed complete response) requires disappearance of all target lesions; PR (partial response) requires \>=50% decrease in the sum of the products of the greatest diameters; Overall Response (OR)=CR/CRu+PR.
Time frame: up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Chemosensitive) | Objective Overall Response Rate | 14 participants |
| Cohort 2 (Chmoresistant) | Objective Overall Response Rate | 0 participants |
p-value: 0.022Fisher Exact
Primary
Safety and Toxicity of Ixabepilone
Number of patients experiencing adverse event grade 3 or above. Grade was determined by the National Cancer Institute Common Toxicity Criteria (CTC) version 2.0. Adverse events possibly, probably, or definitely attributed to use of ixabepilone.
Time frame: up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Chemosensitive) | Safety and Toxicity of Ixabepilone | 27 participants |
| Cohort 2 (Chmoresistant) | Safety and Toxicity of Ixabepilone | 8 participants |
p-value: 1Fisher Exact
Secondary
Duration of Response
Duration of response was measured from the time measurement criteria are met for CR(complete response)/CRu(unconfirmed complete response)/PR(partial response), whichever was first recorded, until the first date that PD(progressive disease) was objectively documented. According to the 1999 international response criteria as published by Cheson, CR/CRu is defined as the disappearance of all target lesions; PR is defined as \>=50% decrease in the sum of the products of the greatest diameters; PD is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy.
Time frame: up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Chemosensitive) | Duration of Response | 291 Days |
Secondary
Overall Survival
Defined as the time from the first day of therapy to the date of death. If the patient was lost to follow-up, survival was censored on the last date the patient was known to be alive.
Time frame: up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Chemosensitive) | Overall Survival | 501 Days |
| Cohort 2 (Chmoresistant) | Overall Survival | 98 Days |
p-value: 0.695Log Rank
Secondary
Time to Progression
Defined as the time from the first day of treatment until the date PD(progressive disease) or death is first reported. Patients who died without a reported prior progression was considered to have progressed on the day of their death. Patients who did not progress was censored at the day of their last tumor assessment. According to the 1999 international response criteria as published by Cheson, progression/progressive disease is defined as \>=50% increase from nadir in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or nonresponders, or appearance of any new lesion during or at the end of therapy.
Time frame: up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 (Chemosensitive) | Time to Progression | 112 Days |
| Cohort 2 (Chmoresistant) | Time to Progression | 84 Days |
p-value: 0.55Log Rank