Phase 2
N=65
Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma
Recurrent Mantle Cell Lymphoma · Recurrent Non-Hodgkin Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT00703664 ↗Enrolled (actual)
65
Serious AEs
49.2%
Results posted
Aug 2018
Primary outcome: Primary: Overall Response Rate (ORR) — 31.8; 0; 7.7 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Bortezomib (Drug); Laboratory Biomarker Analysis (Other); Vorinostat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Dec 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) |
31.8; 0; 7.7 | — |
| SECONDARY Best Response |
7; 0; 3; 5; 2; 8 | — |
| SECONDARY Progression-free Survival (PFS) |
7.6; 1.8 | — |
| SECONDARY Duration of Partial Response |
4.2; 2.1 | — |
| SECONDARY Duration of Stable Disease |
3.8; 3.8; 1.3 | — |
Summary
This phase II trial studies how well bortezomib and vorinostat work in treating patients with recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed mantle cell or diffuse large B-cell lymphoma; histological material must be available for central pathological review; unstained histological material -- slides or blocks -- must be available for correlative studies; archived material from previous biopsies is acceptable, unless a patient's lymphoma has been known to undergo histological transformation in the past, in which case a repeat biopsy to confirm histology prior to enrollment is required; availability of material must be confirmed at the time of registration, but material may be submitted subsequent to registration and initiation of study treatment
- Measurable disease according to the Revised Response Criteria for Malignant Lymphoma; this requires at least one lesion greater than 1.0 cm in diameter in both the long and short axis as measured by spiral computed tomography (CT) scan or physical exam
- Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
- >= 6 months have elapsed since allogeneic transplant
- No graft vs. host disease (GVHD) is present
- Not currently on immunosuppressive therapy
- Prior therapy:
- Mantle cell lymphoma:
- Previously treated or untreated
- No prior bortezomib
- Diffuse large B-cell lymphoma:
- At least one prior systemic therapy
- No prior bortezomib
- Note: Not intended for patients in first relapse who are candidates for high dose therapy with stem cell support
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Able to tolerate loperamide or other anti-diarrheal medications
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 75 x 10^9/L
- Total bilirubin = = 60 mL/min according to the Cockcroft-Gault formula
- For patients with known human immunodeficiency virus (HIV) infection, a cluster of differentiation (CD)4 count >= 0.5 x 10^9/L
- For patients whose last treatment included bendamustine or fludarabine, a CD4 count >= 0.4 x 10^9/L
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and to report pregnancy or suspected pregnancy while participating in the study
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
- Chemotherapy or large field radiotherapy within 3 weeks prior to entering the study
- Prior histone deacetylase inhibitor as cancer treatment
- Concurrent treatment with other investigational agents
- Plans for other concurrent cancer treatment; if steroids for cancer control have been used, patients must be off these agents for >= 1 week before starting treatment; exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose = 2 neuropathy, regardless of cause
- Unable to take oral medications
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib or vorinostat
- Not sufficiently recovered from previous treatment
- Medical or other condition (for example: uncontrolled infection; potentially life threatening changes on electrocardiogram [EKG]) or concurrent treatment (for example, marrow suppressive agents such as zidovudine) that represents an inappropriate risk to the patient or likely would compromise achievement of the primary study objective; patients should be closely monitored when given bortezomib in combination with the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and inducers
- Pregnant women are excluded from this study; breastfeeding should be discontinued
- Active concurrent malignancy, except adequately treated non-melanoma skin cancer
Data sourced from ClinicalTrials.gov (NCT00703664). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.