NCT00992446

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

Completed Phase 2 Results posted Last updated 18 March 2020

What this trial tests

Phase 2 trial testing Autologous Hematopoietic Stem Cell Transplantation in Adult Diffuse Large B-Cell Lymphoma in 27 participants. Completed in 29 October 2019.

Timeline

2 September 2010

Primary endpoint
17 June 2015

29 October 2019

Quick facts

Lead sponsor	Fred Hutchinson Cancer Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	27
Start date	2 September 2010
Primary completion	17 June 2015
Estimated completion	29 October 2019
Sites	1 location across United States

Drugs / interventions tested

• Autologous Hematopoietic Stem Cell Transplantation
• Bortezomib (bortezomib) — full drug profile →
• Carmustine (CARMUSTINE) — full drug profile →
• Cytarabine — full drug profile →
• Etoposide (etoposide) — full drug profile →
• Melphalan
• Rituximab — full drug profile →
• Vorinostat

Conditions studied

• Adult Diffuse Large B-Cell Lymphoma — all drugs for Adult Diffuse Large B-Cell Lymphoma →
• B-Cell Non-Hodgkin Lymphoma — all drugs for B-Cell Non-Hodgkin Lymphoma →
• Follicular Lymphoma — all drugs for Follicular Lymphoma →
• Mantle Cell Lymphoma — all drugs for Mantle Cell Lymphoma →

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Adult Diffuse Large B-Cell Lymphoma or B-Cell Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant Primary · 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 Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	19

Median Time to Disease Progression Secondary · time post ASCT to progression

median days from transplant to relapse/progression

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	1.05	0.41 – 8.05

Ability to Complete Planned 12 Cycles of Maintenance Therapy Secondary · Approximately 12 months following start of maintenance therapy

Number of patients who completed all 12 cycles of maintenance therapy.

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	7
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	3
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	2
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	5

Overall Survival Secondary · 6.64 Years Post-Transplant

Number of patients alive who received maintenance therapy

Alive

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	16

Dead

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	3

Event-free Survival Secondary · 6.64 Years Post-Transplant

Number of patients alive without disease progression/relapse

Alive without disease porgression

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	14

alive with disease progression

Group	Value	95% CI
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))	5

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))

Serious: 9/27 (33%)

Deaths: 7/27

Serious adverse events (6 terms)

Reaction	System	Treatment (Chemotherapy, A…
Atrial flutter/atrial fibrillation	Cardiac disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Pneumonia	Infections and infestations	—
Nausea, vomiting, and diarrhea requiring hospitalization	Gastrointestinal disorders	—
Abdominal pain/diarrhea	Gastrointestinal disorders	—
Colitis	Gastrointestinal disorders	—

Other adverse events (20 terms — click to expand)

Reaction	System	Treatment (Chemotherapy, A…
Neutropenia	Investigations	—
Thrombocytopenia	Investigations	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Mucositis	Gastrointestinal disorders	—
Neutropenia	Investigations	—
Nausea/Vomitting	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Anemia	Blood and lymphatic system disorders	—
Dehydration	Metabolism and nutrition disorders	—
Auto GVHD	General disorders	—
Colitis	Gastrointestinal disorders	—
Heartburn	Gastrointestinal disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Volume overload	General disorders	—
Peripheral neuropathy	Nervous system disorders	—
Thrombocytopenia	Investigations	—
Dizziness	Nervous system disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Methemoglobinemia	Blood and lymphatic system disorders	—

Most-reported serious reactions: Atrial flutter/atrial fibrillation, Febrile neutropenia, Pneumonia, Nausea, vomiting, and diarrhea requiring hospitalization, Abdominal pain/diarrhea, Colitis.

Data from ClinicalTrials.gov NCT00992446 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
   Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
2. Histone deacetylase inhibitors: clinical implications for hematological malignancies.
   Tambaro FP, Dell'aversana C, Carafa V, Nebbioso A, et al · · 2010 · cited 13× · PMID 22704087 · DOI 10.1007/s13148-010-0006-2
3. Histone Modifications and Their Targeting in Lymphoid Malignancies.
   Fernández-Serrano M, Winkler R, Santos JC, Le Pannérer MM, et al · · 2021 · cited 10× · PMID 35008680 · DOI 10.3390/ijms23010253
4. Epigenetic Therapy as a Putative Molecular Target to Modulate B Cell Biology and Behavior in the Context of Immunological Disorders.
   da Costa TP, El-Cheikh MC, Carneiro K. · · 2020 · cited 7× · PMID 32090127 · DOI 10.1155/2020/1589191
5. Strategies to improve outcomes of autologous hematopoietic cell transplant in lymphoma.
   Dahi PB, Lazarus HM, Sauter CS, Giralt SA. · · 2019 · cited 7× · PMID 30390059 · DOI 10.1038/s41409-018-0378-z
6. Impact of Histone Modifications and Their Therapeutic Targeting in Hematological Malignancies.
   Markouli M, Strepkos D, Piperi C. · · 2022 · cited 5× · PMID 36362442 · DOI 10.3390/ijms232113657
7. Epigenetic targets in B- and T-cell lymphomas: latest developments.
   Ribeiro ML, Sánchez Vinces S, Mondragon L, Roué G. · · 2023 · cited 3× · PMID 37273421 · DOI 10.1177/20406207231173485
8. Bortezomib in mantle cell lymphoma: comparative therapeutic outcomes.
   Vallumsetla N, Paludo J, Kapoor P. · · 2015 · cited 2× · PMID 26609233 · DOI 10.2147/tcrm.s72943