Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00992446
First received: October 7, 2009
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This phase II trial is studying the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma (NHL) after an autologous stem cell transplant (ASCT). Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die. Giving bortezomib together with vorinostat after an ASCT may thus kill any lymphoma cells that remain after transplant.


Condition Intervention Phase
Anaplastic Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Contiguous Stage II Mantle Cell Lymphoma
Grade 1 Follicular Lymphoma
Grade 2 Follicular Lymphoma
Grade 3 Follicular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Stage I Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Mixed Cell Lymphoma
Stage I Adult Diffuse Small Cleaved Cell Lymphoma
Stage I Adult T-cell Leukemia/Lymphoma
Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
Stage I Grade 1 Follicular Lymphoma
Stage I Grade 2 Follicular Lymphoma
Stage I Grade 3 Follicular Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Mycosis Fungoides/Sezary Syndrome
Stage II Adult T-cell Leukemia/Lymphoma
Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
Stage II Mycosis Fungoides/Sezary Syndrome
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Drug: rituximab
Drug: carmustine
Drug: cytarabine
Drug: etoposide
Drug: melphalan
Drug: bortezomib
Drug: vorinostat
Procedure: autologous hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bortezomib* and Vorinostat as Maintenance Therapy After Autologous Transplant for Non-Hodgkin's Lymphoma Using R-BEAM or BEAM Conditioning Transplant Regimen

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Toxicity of maintenance therapy with bortezomib and vorinostat [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Grade of toxicity will be per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.


Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2009
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, monoclonal antibody, transplant)
All patients receive carmustine IV over 3 hours on day -7; cytarabine IV twice daily over 3 hours and etoposide IV twice daily over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with CD20+ lymphoma 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 once daily on days 1-14 of 28-day cycle. Treatment with bortezomib and vorinostat repeats for total of 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess toxicities of combining vorinostat and bortezomib as maintenance therapy after ASCT for NHL.

SECONDARY OBJECTIVES:

I. Ability to complete planned therapy.

II. Time to disease progression and event-free survival.

III. Overall survival.

OUTLINE:

All patients receive carmustine intravenously (IV) over 3 hours on day -7; cytarabine IV twice daily over 3 hours and etoposide IV twice daily over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with cluster of differentiation (CD)20+ lymphoma 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 on days 1-14 of 28-day cycle. Treatment with bortezomib and vorinostat repeats for total of 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for at least 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion Criteria for Autologous Transplant:
  • Diagnosis of NHL, 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 (ECG)
  • Total bilirubin (TB) =< 1.5 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3x the upper limit of normal (ULN)
  • Creatinine clearance (CrCL) (calculated creatinine clearance is permitted) > 40 mL/min
  • Diffusing capacity of 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 post menopausal, 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 NHL
  • 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
  • TB =< 1.5 x ULN
  • AST/ALT =< 2.5 x ULN

Exclusion Criteria:

  • Exclusion Criteria for 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 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 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 diabetes mellitus (DM)
  • Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT
  • Untreated systemic infection
  • Potassium (K) and magnesium (Mg) >= grade2 toxicity
  • Patient had MI 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 ECG abnormality at screening must be documented by the investigator as not medically relevant
  • Patient has hypersensitivity to VELCADE, boron, or mannitol
  • Female subject is pregnant or lactating; confirmation that the subject is not pregnant must be established by a negative serum 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00992446

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Leona A. Holmberg    206-667-6447      
Principal Investigator: Leona A. Holmberg         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Leona Holmberg Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00992446     History of Changes
Other Study ID Numbers: 2292.00, NCI-2009-01302, P30CA015704
Study First Received: October 7, 2009
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
Autologous stem cell transplant
NHL
maintenance therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Mycoses
Mycosis Fungoides
Sezary Syndrome
Syndrome
Disease
Immune System Diseases
Immunoproliferative Disorders
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Antibodies, Monoclonal
Bortezomib
Carmustine
Cytarabine

ClinicalTrials.gov processed this record on November 25, 2014