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Phase 2 N=65 Treatment

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

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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