Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00992446
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 27
• Location: 1
• Arm: 1
• Actual Duration (Months): 109.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Diffuse Large B-Cell Lymphoma; B-Cell Non-Hodgkin Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin Lymphoma; T-Cell Non-Hodgkin Lymphoma	Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Bortezomib; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Melphalan; Drug: Rituximab; Drug: Vorinostat	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Assess toxicities of combining vorinostat and bortezomib as maintenance therapy after autologous stem cell transplant (ASCT) for NHL.

SECONDARY OBJECTIVES:

1. Ability to complete planned therapy.

2. Time to disease progression, event-free survival.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bortezomib* and Vorinostat as Maintenance Therapy After Autologous Transplant for Non-Hodgkin Lymphoma Using R-BEAM or BEAM Conditioning Transplant Regimen
• Actual Study Start Date: Sep 2, 2010
• Actual Primary Completion Date: Jun 17, 2015
• Actual Study Completion Date: Oct 29, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo ASCT; Other Names: Autologous Stem Cell Transplantation ; Drug: Bortezomib; Given IV; Other Names: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid LDP 341 MLN341 PS-341 PS341 Velcade ; Drug: Carmustine; Given IV; Other Names: BCNU Becenum Becenun BiCNU Bis(chloroethyl) Nitrosourea Bis-Chloronitrosourea Carmubris Carmustin Carmustinum FDA 0345 Gliadel N,N'-Bis(2-chloroethyl)-N-nitrosourea Nitrourean Nitrumon SK 27702 SRI 1720 WR-139021 ; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Drug: Rituximab; Given IV; Other Names: BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar BI 695500 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 RTXM83 ; Drug: Vorinostat; Given PO; Other Names: L-001079038 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Median Time to Disease Progression [time post ASCT to progression]

   median days from transplant to relapse/progression

2. 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.

3. Overall Survival [6.64 Years Post-Transplant]

   Number of patients alive who received maintenance therapy

4. Event-free Survival [6.64 Years Post-Transplant]

   Number of patients alive without disease progression/relapse

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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:

• EXCLUSION CRITERIA FOR AUTOLOGOUS TRANSPLANT

• Karnofsky performance score < 70%

• Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement)

• Pregnant or breastfeeding

• Fertile men and women unwilling to use contraceptive techniques from the time of transplant until one month post maintenance therapy

• Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)

• Patients with evidence of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow examination

• Prolonged corrected QT interval (QTC) on electrocardiogram (EKG)

• Poorly-controlled diabetes mellitus (DM)

• = grade 2 peripheral neuropathy

• Prior history of human immunodeficiency virus (HIV) positivity or known history of hepatitis B or C

• Previous history of hypersensitivity to bortezomib, boron, or mannitol; known hypersensitivity to the components of study drug or its analogs

• Require therapeutic anticoagulation treatment, especially with Coumadin

• Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) or who has not recovered from adverse events due to agents administered more than 30 days earlier

• Patient is currently participating or has participated in a study with an investigational compound or devise within 30 days of initial dosing with study drug(s)

• Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period

• History of central nervous system (CNS) disease

• Symptomatic ascites or pleural effusions

• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

• Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse

• Patient with a history of a prior malignancy with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma or an in situ malignancy; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician

• Patient has a history or current evidence of any condition, therapy, or laboratory (lab) abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate

• Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs

• EXCLUSION CRITERIA FOR MAINTENANCE THERAPY

• = grade 2 peripheral neuropathy within 14 days before beginning maintenance therapy

• Prolonged QTC

• Poorly-controlled DM

• Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT

• Untreated systemic infection

• Potassium (K) and magnesium (Mg) >= grade 2 toxicity

• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant

• Patient has hypersensitivity to VELCADE (bortezomib), boron, or mannitol

• Female subject is pregnant or lactating; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women

• Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on day 1 before first dose of study drug, if applicable

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial

• Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Leona Holmberg, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00992446
• Other Study ID Numbers: 2292.00; NCI-2009-01302; FH 2292/X05287; X05287; 2292.00; P30CA015704
• First Posted: Oct 9, 2009
• Last Update Posted: Mar 18, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center: Autologous stem cell transplant; NHL; maintenance therapy
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Cytarabine; Rituximab; Antineoplastic Agents, Immunological; Etoposide; Bortezomib; Etoposide phosphate; Melphalan; Mechlorethamine; Vorinostat; Carmustine; Podophyllotoxin; Nitrogen Mustard Compounds; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Period Title: Overall Study
STARTED	27
COMPLETED	19
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Overall Participants	27
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 59.3%
>=65 years	11 40.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	7 25.9%
Male	20 74.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.7%
Not Hispanic or Latino	26 96.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.7%
White	26 96.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Measure Participants	19
Count of Participants [Participants]	19 70.4%

2. Secondary Outcome

Title	Median Time to Disease Progression
Description	median days from transplant to relapse/progression
Time Frame	time post ASCT to progression

Outcome Measure Data

Analysis Population Description

median time to progression /relapse

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Measure Participants	19
Median (Full Range) [years]	1.05

3. Secondary Outcome

Title	Ability to Complete Planned 12 Cycles of Maintenance Therapy
Description	Number of patients who completed all 12 cycles of maintenance therapy.
Time Frame	Approximately 12 months following start of maintenance therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Measure Participants	19
Completed 12 Cycles of Maintenance Therapy	7 25.9%
Unable to complete therapy due to relapse	3 11.1%
Withdrawl at patient request	2 7.4%
Unable to complete due to toxicities	5 18.5%
PI decision due to increasing creatinine levels	1 3.7%
Patient left state	1 3.7%

4. Secondary Outcome

Title	Overall Survival
Description	Number of patients alive who received maintenance therapy
Time Frame	6.64 Years Post-Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Measure Participants	19
Alive	16 59.3%
Dead	3 11.1%

5. Secondary Outcome

Title	Event-free Survival
Description	Number of patients alive without disease progression/relapse
Time Frame	6.64 Years Post-Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
Measure Participants	19
Alive without disease porgression	14 51.9%
alive with disease progression	5 18.5%

Adverse Events

Adverse Event Reporting Description	Adverse events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0., except hematological toxicity. Grade 3 or higher reported.
Arm/Group Title	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Arm/Group Description	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
All Cause Mortality
	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
	Affected / at Risk (%)	# Events
Total	7/27 (25.9%)
Serious Adverse Events
	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
	Affected / at Risk (%)	# Events
Total	9/27 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	2/27 (7.4%)
Cardiac disorders
Atrial flutter/atrial fibrillation	2/27 (7.4%)
Gastrointestinal disorders
Abdominal pain/diarrhea	1/27 (3.7%)
Nausea, vomiting, and diarrhea requiring hospitalization	2/27 (7.4%)
Colitis	1/27 (3.7%)
Infections and infestations
Pneumonia	2/27 (7.4%)
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
	Affected / at Risk (%)	# Events
Total	27/27 (100%)
Blood and lymphatic system disorders
Anemia	3/27 (11.1%)
Febrile neutropenia	21/27 (77.8%)
Methemoglobinemia	1/19 (5.3%)
Gastrointestinal disorders
Colitis	2/27 (7.4%)
Diarrhea	6/27 (22.2%)
Heartburn	2/27 (7.4%)
Nausea/Vomitting	7/27 (25.9%)
Nausea	6/27 (22.2%)
Mucositis	16/27 (59.3%)
General disorders
Auto GVHD	2/27 (7.4%)
Volume overload	2/27 (7.4%)
Investigations
Neutropenia	27/27 (100%)
Thrombocytopenia	27/27 (100%)
Neutropenia	13/19 (68.4%)
Thrombocytopenia	2/19 (10.5%)
Metabolism and nutrition disorders
Dehydration	3/27 (11.1%)
Hyponatremia	1/19 (5.3%)
Nervous system disorders
Dizziness	1/19 (5.3%)
Peripheral neuropathy	2/19 (10.5%)
Skin and subcutaneous tissue disorders
Rash	2/27 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.