Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
Conditions
Brief summary
FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES: I. Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma. II. Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients. III. Determine 2-year progression-free and overall survival. OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3-6 months for up to 5 years.
Interventions
DRUGromidepsin
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 B-cell non-Hodgkin's lymphoma of 1 of the following subtypes: * Mantle cell lymphoma * Diffuse large cell lymphoma * (Ineligible for or unwilling to undergo stem cell transplantation) * Relapsed or refractory disease: * Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation * No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease * Measurable disease, defined as \>= 1 lesion \>= 1.5 cm in the longest diameter * No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma) * ECOG performance status 0-2 * Absolute neutrophil count \>= 1,000/mm\^3 OR \>= 500/mm\^3 if extensive bone marrow involvement (\> 50%) or hypersplenism with palpable splenomegaly * Platelet count \>= 75,000/mm\^3 OR \>= 50,000/mm\^3 if extensive bone marrow involvement (\> 50%) or hypersplenism with palpable splenomegaly * Bilirubin normal * Alkaline phosphatase =\< 2 times upper limit of normal (ULN) * AST =\< 2 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure * No history of serious ventricular arrhythmia * QTc \< 500 msec * No evidence of cardiac hypertrophy on ECG * No known HIV positivity * No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes) * Recovered from prior therapy * No prior doxorubicin hydrochloride \>= 450 mg/m\^2 or mitoxantrone \>= 112 mg/m\^2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a doxorubicin equivalent dose \< 450 mg/m\^2 * No prior therapy with a histone deacetylase inhibitor * No concurrent dexamethasone or prednisone except for refractory nausea/vomiting * No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate) * Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic) * No CNS lymphoma * Creatinine normal * Cardiac function \>= 50% by MUGA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment | 24 weeks (6 courses of 4 week cycles) | International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free-survival (PFS) | 2 Years | Time to disease progression is defined as the time from registration to documentation of disease progression. |
| Median Overall Survival | 5 Years | Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: September 20, 2006 to May 08, 2009. All recruitment done at UT MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| FR901228 13 mg/m\^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15 | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | FR901228 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 66.8 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 6 / 9 |
Outcome results
Primary
Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment
International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - ≥50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen.
Time frame: 24 weeks (6 courses of 4 week cycles)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FR901228 | Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment | Complete Response | 0 participants |
| FR901228 | Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment | Partial Response | 1 participants |
Secondary
Median Overall Survival
Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier.
Time frame: 5 Years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FR901228 | Median Overall Survival | 20 months |
Secondary
Median Progression Free-survival (PFS)
Time to disease progression is defined as the time from registration to documentation of disease progression.
Time frame: 2 Years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FR901228 | Median Progression Free-survival (PFS) | 4 months |