Venetoclax Plus R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Conditions

• Diffuse Large B-cell-lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Venetoclax — DRUG
  Beginning with 400mg daily on days 1-10 of cycle 1-3 Phase I dose escalation scheme: Dose Level -2 (DL-2): 100 mg daily, days 1-10, cycle 1-3 DL-1: 200 mg daily, days 1-10, cycle 1-3 DL1: 400 mg daily, days 1-10, cycle 1-3 DL2: 600 mg daily, days 1-10, cycle 1-3 DL3: 800 mg daily, days 1-10, cycle 1-3 Phase II: Given at a dose of 400mg daily for 5 days
• Rituximab — DRUG
  Part of R-ICE treatment: Rituximab: 375 mg/m\^2 intravenously (IV) on Day 1 of R-ICE every 21 days
• Ifosfamide — DRUG
  Part of R-ICE treatment: Ifosfamide: 5,000 mg/m\^2 mixed together with mesna at a dose of 5,000 mg/m\^2 over 24 hours beginning on Day 2 and completing on Day 3 of each 21-day cycle
• Carboplatin — DRUG
  Part of R-ICE treatment: Carboplatin: At a dose corresponding to an AUC = 5 based on Cockcroft-Gault calculation of GFR using adjusted body weight. Carboplatin is given IV on the Day 2 of RICE of each 21 day cycle
• Etoposide — DRUG
  Part of R-ICE treatment: Etoposide: 100 mg/m2by IV daily on 3 consecutive days (Days 1-3) of each 21-day cycle

Study Details

The purpose of this study is to determine the correct dose and safety of adding a new cancer drug, venetoclax, to a standard combination of chemotherapy drugs as a second treatment for relapsed/refractory DLBCL. In this study, venetoclax will be added to RICE (rituximab, ifosfamide, carboplatin, etoposide), a common set to cancer drugs used as a second line treatment for relapsed/refractory DLBCL. Venetoclax, is a new targeted anti-cancer drug, which works by mimicking a particular protein produced by the tumor and interrupting its normal processes, ultimately causing the tumor cells to die. Adding venetoclax to the standard RICE regimen is believed to increase the chance of getting cancer into remission. Venetoclax is experimental because it is not approved by the Food and Drug Administration (FDA) for the treatment of relapsed/refractory DLBCL. Venetoclax has been FDA approved for use in patients with chronic lymphocytic leukemia (CLL).

Key Dates

Start date

Jun 26, 2017

Status verified

Nov 2022

Primary completion

Aug 12, 2022

Completion

Aug 12, 2023

Study Design

Enrollment

65 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: V+RICE
  Venetoclax given in combination with R-ICE chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide) Phase I part of this study is a 3 + 3 design, with 3 dose levels, a minimum of 6 participants (maximum of 18) will be required to identify the recommended phase 2 dose (RP2D). Phase II involvs two stages: In stage I, a total of 16 participants will be accrued. If there are 7 or fewer complete responses (CR), the study will be stopped. Otherwise, an additional 30 participants will be accrued in stage II. The maximum number of treatment cycles with V+RICE is three. Participants who achieve complete remission at the interim response assessment after 2 cycles may omit cycle 3 in order to proceed to subsequent consolidation therapy with autologous stem cell transplant (AHSCT). Participants will proceeed to other treatment including RICE, other chemotherapy, peripheral blood stemm cell collection, and ASCT per institutional guidelines.

Primary Outcome Measure

Recommended Phase II Dose [ Time Frame: Up to 12 weeks ]

Locations (3)

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