Lymphoma
Conditions
Keywords
contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, noncontiguous stage II marginal zone lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, recurrent mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma
Brief summary
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving vorinostat together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects of giving vorinostat together with rituximab and to see how well it works in treating patients with indolent non-Hodgkin lymphoma.
Detailed description
OBJECTIVES: * To evaluate the anti-tumor activity of vorinostat and rituximab, in terms of objective response rate, time to progression, and survival, in patients with indolent non-Hodgkin lymphoma. * To assess the toxicity profile of this regimen in these patients. OUTLINE: Patients receive oral vorinostat twice daily on days 1-14 and rituximab IV on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.
Interventions
BIOLOGICALrituximab
Rituximab will be administered at a dose of 375 mg/m2 on day 1 of every cycle, every 3 weeks.
DRUGvorinostat
200 mg twice daily, orally for 14 days followed by a seven day break on a 21 day cycle.
Sponsors
National Cancer Institute (NCI)
Merck Sharp & Dohme LLC
City of Hope Medical Center
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
Patients must have histologically or cytologically confirmed indolent Non-Hodgkin's Lymphoma; included in this category are newly diagnosed or relapsed/refractory follicular center lymphomas grade I, II, III, relapsed/refractory marginal zone B-cell lymphoma (nodal and extranodal), relapsed/refractory mantle cell lymphoma Patients must have measurable disease by computed tomography (CT) scan; positron emission tomography (PET) scan evaluations are desirable but not mandatory, so that patients with negative PET scans but measurable disease by CT are eligible Patients may have had up to four prior chemotherapeutic regimens; steroids alone and local radiation do not count as regimens (radiotherapy must have been completed at least 14 days prior to starting vorinostat); Rituxan alone does not count as a regimen; however, Bexxar or Zevalin do; for treated patients, the most recent therapy must have failed to induce a complete response (i.e., there is persistent disease by CT or PET), or there must be disease progression or recurrence after the most recent therapy Patients may be enrolled who relapse after autologous stem cell transplant if they are at least three months after transplant, and after allogeneic transplant if they are at least six month post transplant; to be eligible after either type of transplant, patients should have no active related infections (i.e., fungal or viral); in the case of allogeneic transplant relapse, there should be no active acute graft versus host disease (GvHD) of any grade, and no chronic graft versus host disease other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression Life expectancy of greater than 3 months Eastern Cooperative Oncology Group (ECOG) performance status 2 (Karnofsky \>= 60%) Absolute neutrophil count \>= 1,000/mcL Platelets \>= 100,000/mcL Total bilirubin within normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal Creatinine up to and including 2 mg/dl Pre-menopausal women must have a negative serum pregnancy test prior to entry on this study; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
Patients who have had chemotherapy within 4 weeks, or radiotherapy within 2 weeks or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include use of steroids, which may continue until two days prior to enrollment; low dose chlorambucil should be stopped two weeks prior to beginning vorinostat; valproic acid should be stopped at least two weeks prior to enrollment; nitrosoureas and mitomycin should be stopped 6 weeks prior to enrollment Patients may not be receiving any other investigational agents Patients with known brain metastases are excluded from this clinical trial unless the metastases are controlled after therapy and have not been treated with steroids within the past two months History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat There must be no plans for the patient to receive concurrent hormonal, biological, or radiation therapy Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if mother is treated with vorinostat Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible; in addition, HIV patients not receiving combination antiretroviral therapy are also ineligible Patients with other active malignancies are ineligible for this study Patients with preexisting or previous coagulation issues are not excluded from study as long as 1) previous pulmonary embolism or deep vein thrombosis have been adequately treated or 2) if they are actively receiving Coumadin or lovenox for anticoagulation; patients who are already on coumadin or lovenox do not need to take additional 40 mg subcutaneous injections daily
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (Complete and Partial Response) | After every 3 cycles, up to 1 year after the start of treatment | Response was assessed according to the 2007 Cheson criteria using CT scans or PET: Complete Response (CR), Disappearance of all evidence of disease; Partial Response (PR), \>=50% decrease in the Sum of the Product of Diameters (SPD) of up to 6 largest dominant masses and no increase in the size of other nodes; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Until disease progress\relapse, up to 1 year after the start of treatment | Progression\\Relapse is defined using the 2007 Cheson criteria, as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy; or at least a 50% increase for nadir in the SPD of any previously involved nodes; or at least a 50% increase in the longest diameter of any singe previously identified node more than 1 cm in its short axis. Estimated using the product-limit method of Kaplan and Meier. |
| Number of Participants With Grade 3 and 4 Toxicities | 3 weeks after the stop of treatment | Grade 3 & 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 3.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat and Rituximab Vorinostat by mouth 2X per day for two weeks followed by one week of rest. Rituximab intravenously once every three weeks .
rituximab: Rituximab will be administered at a dose of 375 mg/m2 on day 1 of every cycle, every 3 weeks.
vorinostat: 200 mg twice daily, orally for 14 days followed by a seven day break on a 21 day cycle. | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | found to be ineligible after starting tx | 2 |
Baseline characteristics
| Characteristic | Vorinostat and Rituximab |
|---|---|
| Age, Continuous | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 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 | 25 Participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 13 / 30 |
Outcome results
Primary
Overall Response Rate (Complete and Partial Response)
Response was assessed according to the 2007 Cheson criteria using CT scans or PET: Complete Response (CR), Disappearance of all evidence of disease; Partial Response (PR), \>=50% decrease in the Sum of the Product of Diameters (SPD) of up to 6 largest dominant masses and no increase in the size of other nodes; Overall Response (OR) = CR + PR.
Time frame: After every 3 cycles, up to 1 year after the start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat and Rituximab | Overall Response Rate (Complete and Partial Response) | 46 percentage of participants |
Secondary
Number of Participants With Grade 3 and 4 Toxicities
Grade 3 & 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 3.0.
Time frame: 3 weeks after the stop of treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Serum phosphate decreased | 3 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Serum potassium decreased | 2 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Syncope | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Hypoxia | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Neutrophil count decreased | 3 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Platelet count decreased | 5 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Hemoglobin decreased | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Lymphocyte count decreased | 7 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Hypotension | 2 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Chills | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Fatigue | 9 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Dehydration | 3 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Diarrhea | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Kidney infection | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Pneumonia | 2 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Sepsis | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Urinary tract infection | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Localized edema | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Alanine aminotransferase increased | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Aspartate aminotransferase increased | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Blood glucose increased | 3 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Muscle weakness | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Pneumonitis | 1 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Thrombosis | 4 Participants |
| Vorinostat and Rituximab | Number of Participants With Grade 3 and 4 Toxicities | Vascular access complication | 1 Participants |
Secondary
Progression-free Survival
Progression\\Relapse is defined using the 2007 Cheson criteria, as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy; or at least a 50% increase for nadir in the SPD of any previously involved nodes; or at least a 50% increase in the longest diameter of any singe previously identified node more than 1 cm in its short axis. Estimated using the product-limit method of Kaplan and Meier.
Time frame: Until disease progress\relapse, up to 1 year after the start of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vorinostat and Rituximab | Progression-free Survival | 29.2 Months |