Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma
Conditions
Brief summary
This phase II trial is studying how well PXD101 works in treating patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. PXD101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.
Detailed description
PRIMARY OBJECTIVES: I. Evaluate response rate in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma treated with PXD101. SECONDARY OBJECTIVES: I. Determine the toxicity of this drug in these patients. II. Estimate the 6-month progression-free survival rate in patients treated with this drug. TERTIARY OBJECTIVES: I. Determine the major histocompatability complex of class II proteins (HLA-DR, -DP, -DQ), TUNEL, and CD8 infiltration status, by immunochemistry on paired pre- and post-treatment tumor samples, in the first 20 patients enrolled. II. Measure CIITA and HLA-DR mRNA expression using quantitative reverse transcriptase-polymerase chain reaction and determine, preliminarily, the associations of these markers with progression-free survival. III. Evaluate paired pre- and post-treatment peripheral blood mononuclear cells from patients for histone acetylation status and determine correlation with findings from duplicate experiments on pre- and post-needle core biopsies. OUTLINE: This is a multicenter study. Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Needle core biopsies and peripheral blood mononuclear cells are obtained from the first 20 patients pre- and post-treatment for biomarker correlative studies. After completion of study treatment, patients are followed every 3-6 months for up to 3 years.
Interventions
DRUGbelinostat
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
* Biopsy-proven (no needle aspirations or cytologies) aggressive B-cell non-Hodgkin's lymphoma (NHL), including 1 of the following histology subtypes: * Diffuse large cell NHL * Burkitt's or Burkitt-like NHL * Primary mediastinal NHL * Relapsed or refractory disease * Bidimensionally measurable disease * Transformed NHL allowed * Not eligible for stem cell transplantation (for patients registered to study at first relapse) * No active CNS involvement by lymphoma * Zubrod performance status 0-2 * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101 * Absolute neutrophil count \>= 1,500/mm\^3 * Platelet count\>=100,000/mm\^3 * WBC \>= 3,000/mm\^3 * Creatinine \< 2 times upper limit of normal (ULN) OR creatinine clearance \>= 60 mL/min * No significant EKG abnormalities * Bilirubin normal * SGOT/SGPT \< 2.5 times ULN (=\< 5 times ULN if liver involvement) * No long QT syndrome or marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of QTc interval \> 500 msec) * No other significant cardiovascular disease, including any of the following: * Unstable angina pectoris * Uncontrolled hypertension * Congestive heart failure related to primary cardiac disease * Any condition requiring anti-arrhythmic therapy * Ischemic or severe valvular heart disease * Myocardial infarction within the past 6 months * No major surgery within 28 days prior to study entry * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent medication that may cause Torsades de Pointes (i.e., prolongation of the QT interval \> 500 msec) * At least 14 days since prior radiotherapy * At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor * No clinical evidence of any of the following: * Severe peripheral vascular disease * Diabetic ulcers or venous stasis ulcers * History of deep venous or arterial thrombosis within the past 3 months * Radioimmunotherapy is considered a chemotherapy regimen * Single-agent rituximab is not considered a chemotherapy regimen * Standard salvage chemotherapy followed by autologous stem cell transplantation is considered 1 regimen * No known AIDS or HIV-associated complex * Not pregnant or nursing * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix * At least 2 weeks since prior therapy and recovered * No more than 5 prior chemotherapy regimens
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) | assessed at week 8, and every 3 months for 3 years | Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | assessed every 3 months for 3 years | Measured from time of registration to death, or last contact date |
| Progression-free Survival | assessed at week 8, then every 3 months for 3 years | Measured from date of registration to time of first documentation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PXD101 Only eligible patients were included in the analyses. Patients receive 1000 mg/m\^2 IV PXD101 on days 1-5 of each 21-day cycle until disease progression. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 1 |
| Overall Study | Ineligible | 1 |
| Overall Study | Lack of Efficacy | 12 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | PXD101 |
|---|---|
| Age, Continuous | 68.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)
Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Time frame: assessed at week 8, and every 3 months for 3 years
Population: All eligible patients who started treatment were included in assessing response estimates.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PXD101 | Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) | No response | 20 participants |
| PXD101 | Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) | Complete Response (CR) | 0 participants |
| PXD101 | Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) | Complete Response Unconfirmed (CRU) | 0 participants |
| PXD101 | Assess Number of Patients Who Achieve Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR) | Partial Response (PR) | 0 participants |
Secondary
Overall Survival
Measured from time of registration to death, or last contact date
Time frame: assessed every 3 months for 3 years
Population: Only eligible patients were included in the analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PXD101 | Overall Survival | 0.9 years |
Secondary
Progression-free Survival
Measured from date of registration to time of first documentation of progression or death, or last contact date. Progression is defined as a 50% increase in sum of products of greatest diameters (SPD) of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; appearance of a new lesion/site; unequivocal progression of non-measurable disease in the opinion of the treating physician; death due to disease without prior documentation of progression.
Time frame: assessed at week 8, then every 3 months for 3 years
Population: Only eligible patients were included in the analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PXD101 | Progression-free Survival | 0.2 years |