Adult Diffuse Large B-Cell Lymphoma, B-Cell Non-Hodgkin Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Non-Hodgkin Lymphoma
Conditions
Keywords
Autologous stem cell transplant, NHL, maintenance therapy
Brief summary
This phase II trial studies the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma (NHL) after patients' own stem cell (autologous) transplant. Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat after an autologous stem cell transplant may thus kill lymphoma cells that remain after transplant.
Detailed description
PRIMARY OBJECTIVES: I. Assess toxicities of combining vorinostat and bortezomib as maintenance therapy after autologous stem cell transplant (ASCT) for NHL. SECONDARY OBJECTIVES: I. Ability to complete planned therapy. II. Time to disease progression, event-free survival. III. Overall survival. OUTLINE: All patients receive carmustine intravenously (IV) over 3 hours on day -7; cytarabine IV twice daily (BID) over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of cluster of differentiation (CD)20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat orally (PO) once daily (QD) on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for at least 2 years.
Interventions
PROCEDUREAutologous Hematopoietic Stem Cell Transplantation
Undergo ASCT
DRUGBortezomib
Given IV
DRUGCarmustine
Given IV
DRUGCytarabine
Given IV
DRUGEtoposide
Given IV
DRUGMelphalan
Given IV
DRUGRituximab
Given IV
DRUGVorinostat
Given PO
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer 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
* INCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT * Diagnosis of non-Hodgkin's lymphoma, transformed B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate for autologous transplant * American Heart Association class I: patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients \> 60 years of age must have a left ventricular ejection fraction of at least \>= 40% demonstrated by multi gated acquisition scan (MUGA) or echocardiogram (Echo) * Total bilirubin =\< 1.5 mg/dL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x the upper limit of normal * Creatinine clearance (CrCL) (calculated creatinine clearance is permitted) \> 40 mL/min * Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) \>= 50% of predicted (corrected for hemoglobin) * Autologous graft with a minimum of \>= 3.0 x 10\^6 CD34+ cells/kg; not CD34 selected * Signed informed consent * Female patients of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG) * Female patient is either postmenopausal, free from menses for \>= 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study * Male patient agrees to use an adequate method of contraception for the duration of the study * INCLUSION CRITERIA FOR MAINTENANCE THERAPY * 30-120 days post ASCT for non-Hodgkin's lymphoma * CrCL \>= 40 ml/min * Platelets (PLT) \>= 75,000 cells/mm\^3 for 5 days after recovery from ASCT nadir * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 for 5 days after recovery from ASCT nadir * Total bilirubin (TB) =\< 1.5 x upper limit of normal (ULN) * AST/ALT =\< 2.5 x ULN
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant | 3 months after start of maintenance therapy | Number of patients on maintenance therapy post-transplant who experienced grade 3 or higher toxicity per NCI-Common Terminology Criteria for Adverse Events, version 3. The first three months of bortezomib and vorinostat therapy will be used as the time period to evaluate toxicity for stopping rules of the study. Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Disease Progression | time post ASCT to progression | median days from transplant to relapse/progression |
| Ability to Complete Planned 12 Cycles of Maintenance Therapy | Approximately 12 months following start of maintenance therapy | Number of patients who completed all 12 cycles of maintenance therapy. |
| Overall Survival | 6.64 Years Post-Transplant | Number of patients alive who received maintenance therapy |
| Event-free Survival | 6.64 Years Post-Transplant | Number of patients alive without disease progression/relapse |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.
Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT
Bortezomib: Given IV
Carmustine: Given IV
Cytarabine: Given IV
Etoposide: Given IV
Melphalan: Given IV
Rituximab: Given IV
Vorinostat: Given PO | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 1 |
| Overall Study | Maintenance Therapy Screen Fail | 5 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 61 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 26 Participants |
| Region of Enrollment United States | 27 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 9 / 27 |
Outcome results
Primary
Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant
Number of patients on maintenance therapy post-transplant who experienced grade 3 or higher toxicity per NCI-Common Terminology Criteria for Adverse Events, version 3. The first three months of bortezomib and vorinostat therapy will be used as the time period to evaluate toxicity for stopping rules of the study. Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).
Time frame: 3 months after start of maintenance therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant | 19 Participants |
Secondary
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Number of patients who completed all 12 cycles of maintenance therapy.
Time frame: Approximately 12 months following start of maintenance therapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | Completed 12 Cycles of Maintenance Therapy | 7 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | Unable to complete therapy due to relapse | 3 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | Withdrawl at patient request | 2 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | Unable to complete due to toxicities | 5 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | PI decision due to increasing creatinine levels | 1 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Ability to Complete Planned 12 Cycles of Maintenance Therapy | Patient left state | 1 Participants |
Secondary
Event-free Survival
Number of patients alive without disease progression/relapse
Time frame: 6.64 Years Post-Transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Event-free Survival | Alive without disease porgression | 14 Participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Event-free Survival | alive with disease progression | 5 Participants |
Secondary
Median Time to Disease Progression
median days from transplant to relapse/progression
Time frame: time post ASCT to progression
Population: median time to progression /relapse
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Median Time to Disease Progression | 1.05 years |
Secondary
Overall Survival
Number of patients alive who received maintenance therapy
Time frame: 6.64 Years Post-Transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Overall Survival | Alive | 16 participants |
| Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat)) | Overall Survival | Dead | 3 participants |