Study of Venetoclax Plus DA-EPOCH-R for the Treatment of Aggressive B-Cell Lymphomas
Condition: Diffuse Large B-Cell Lymphoma; High Grade B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Aggression
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I, open label, single-arm, multi-center, dose-finding study of venetoclax in
      combination with DA-EPOCH-R in patients with aggressive B-Cell Lymphomas.
    

Detailed description: 
      This clinical trial is for men and women with aggressive B-Cell Lymphomas which includes:

        -  Diffuse large B-cell lymphoma (DLBCL),

        -  B-cell lymphoma unclassifiable with intermediate features between DLBCL and Burkitt
           Lymphoma (BL),

        -  High grade B-cell lymphoma (HGBCL),

        -  Transformed indolent NHL (TiNHL). The aggressive B-cell lymphomas enrolling on this
           study have been recognized to have a poor prognosis with the use of conventional
           chemoimmunotherapy. DA-EPOCH-R is an alternative highly effective chemoimmunotherapy
           platform for these lymphomas and may serve as an optimal chemotherapy backbone for the
           incorporation of novel agents such as venetoclax.

      The Bcl-2 protein plays a significant role in the regulation of cell death in malignant
      cells. Overexpression of Bcl-2 family proteins is associated with chemo-resistance of a broad
      variety of cancers, and BCL2 abnormalities are common in aggressive B-cell Lymphomas.
      Venetoclax is a highly selective Bcl-2 family protein inhibitor that binds to Bcl-2 family
      proteins to potentially overcome resistance and enhance responses to therapy. This study has
      been designed to evaluate the safety and preliminary efficacy of venetoclax in combination
      with DA-EPOCH-R.

      Subjects will receive venetoclax in conjunction with six 21-day cycles of DA-EPOCH-R. Dosing
      for DA-EPOCH-R will follow established protocols. Venetoclax will be administered on days 3
      through 12 during cycle 1 and days 1 through 10 of each subsequent cycle. Following
      completion of therapy, subjects will be followed every three months for up to two years.
      Subjects removed from study due to toxicity will be followed until resolution or
      stabilization of the toxicity.
    

Intervention name(s): Venetoclax; Rituximab; Etoposide; Vincristine Sulfate; Cyclophosphamide; Prednisone; Doxorubicin Hydrochloride
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Venetoclax will be administered orally on days 3-12 in cycle 1, and days 1-10 with all subsequent cycles except dose level -1. If dose level -1 is required, venetoclax will be administered on days 3-7 in cycle 1 and 1-5 with subsequent cycles.; Rituximab will be administered as an IV infusion at 375 mg/m2 on day 1 of each cycle of DA-EPOCH-R, immediately prior to the start of chemotherapy. Oral pre-medication 650 mg of acetaminophen and 50-100 mg diphenhydramine hydrochloride will be administered 30 to 60 minutes prior to starting each infusion of rituximab. The first rituximab infusion should be started at 50 mg/hr, and increased in 50-mg/hr increments every 30 minutes to a maximum rate of 400 mg/hr. If this rate of escalation is well tolerated the second and subsequent infusions can begin at a rate of 100 mg/hr and increase in 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. CAUTION: DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.; Etoposide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.; Vincristine Sulfate will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.; Cyclophosphamide will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.; Prednisone will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. Prednisone will be given orally.; Doxorubicin Hydrochloride will be obtained from commercial supply, and will be given for a total of 6 cycles for all patients. The drug will be given by IV route.
Other intervention name(s): Venclexta; Rituxan; IDEC-C2B8; chimeric anti-CD20 monoclonal antibody; VP-16; VePesid; etopophos; toposar; LCR; VCR; cytoxan; Deltasone; Orasone; Paracort; Cortan; Hydroxydaunomycin Hydrochloride; Hydroxydoxorubicin Hydrochloride
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Venetoclax
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: venetoclax; dose-adjusted EPOCH-R; aggressive B-Cell lymphoma; Lymphoma; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; Double hit lymphoma