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

NCT00992446 | Completed Phase 2 Results

• 5 other identifiers: 2292.00NCI-2009-01302FH 2292/X05287X05287P30CA015704
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Adult Diffuse Large B-Cell Lymphoma; B-Cell Non-Hodgkin Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin Lymphoma; T-Cell Non-Hodgkin Lymphoma

Keywords

Autologous stem cell transplant; NHL; maintenance therapy

Outcome Measures

Primary Outcomes (1)

• 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 Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).

  3 months after start of maintenance therapy

Secondary Outcomes (4)

• Median Time to Disease Progression

  time post ASCT to progression

• Ability to Complete Planned 12 Cycles of Maintenance Therapy

  Approximately 12 months following start of maintenance therapy

• Overall Survival

  6.64 Years Post-Transplant

• Event-free Survival

  6.64 Years Post-Transplant

Study Arms (1)

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

EXPERIMENTAL

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; Drug: Bortezomib; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Melphalan; Drug: Rituximab; Drug: Vorinostat

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo ASCT

Also known as: Autologous Stem Cell Transplantation

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Bortezomib DRUG

Given IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Carmustine DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Cytarabine DRUG

Given IV

Also known as: .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

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Melphalan DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Rituximab DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Vorinostat DRUG

Given PO

Also known as: L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (chemotherapy, ASCT, bortezomib, vorinostat))

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell

Interventions

Bortezomib; Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Melphalan; Rituximab; Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Dr. Leona A. Holmberg
• Organization: Fred Hutchinson Cancer Research Center

lholmber@fredhutch.org

206-667-6447

Study Officials

• Leona Holmberg

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 7, 2009
• First Posted: October 9, 2009
• Study Start: September 2, 2010
• Primary Completion: June 17, 2015
• Study Completion: October 29, 2019
• Last Updated: March 18, 2020
• Results First Posted: May 10, 2017

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)