Venetoclax Plus R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03064867|
Recruitment Status : Recruiting
First Posted : February 27, 2017
Last Update Posted : February 9, 2021
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).
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-cell-lymphoma||Drug: Venetoclax Drug: Rituximab Drug: Ifosfamide Drug: Carboplatin Drug: Etoposide||Phase 1 Phase 2|
Establishment of safety of V+RICE in order to identify the recommended Phase II dose (RPD2)
- Determine the overall response rate (ORR) of V+RICE relative to historical controls of RICE alone in r/r DLBCL.
- Determine the proportion of patients who proceed to autologous stem cell transplantation after V+RICE relative to historical controls.
- Describe the progression-free survival (PFS) and overall survival (OS) for patients treated with V + RICE who do and do not proceed to auto-Stem Cell Transplant, relative to historical controls.
- Measure total number of peripheral blood stem cells collected in patients treated with V + RICE who proceed to stem cell mobilization/harvesting, compared to historical controls.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||64 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Venetoclax in Combination With R-ICE (V+RICE) Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma|
|Actual Study Start Date :||June 26, 2017|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||October 2021|
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.
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
Part of R-ICE treatment:
Rituximab: 375 mg/m^2 intravenously (IV) on Day 1 of R-ICE every 21 days
Other Name: Rituxan
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
Other Name: Ifex
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
Other Name: Paraplatin
Part of R-ICE treatment:
Etoposide: 100 mg/m2by IV daily on 3 consecutive days (Days 1-3) of each 21-day cycle
- Recommended Phase II Dose [ Time Frame: Up to 12 weeks ]A maximum of 18 patients can theoretically participate in the initial dose escalation with Retinoic and Lithium, based on 4 dose levels with a maximum of 6 patients at each dose level. At a true dose limiting toxicity rate of 20%, the chance of escalating to the next dose level is 71% and of establishing the lower dose level as maximum tolerated dose is 29%.
- Overall Response Rate [ Time Frame: Up to 12 weeks ]number of patients with complete response or partial response as document in a positron emission tomography/ computerized tomography (PET/CT) scan and defined by the Revised Response Criteria for Malignant Lymphoma
- Proportion of participants Proceeding to ASCT [ Time Frame: Up to 12 weeks ]the number of patients with ASCT divided by the total number of patients
- Progression Free Survival [ Time Frame: Up to 12 weeks ]Average time disease did not progress as based on the Revised Response Criteria for Malignant Lymphoma up to 12 weeks
- Overall Survival [ Time Frame: Up to 12 weeks ]Average time participants are alive from starting treatment to death or 12 weeks, whichever comes first
- Number of Peripheral Blood Stem Cells Collected [ Time Frame: Up to 12 weeks ]Estimated through measurement of CD34+ cells/kg
- Median Number of cluster of differentiation 34 (CD34+) Cells/kg [ Time Frame: Up to 12 weeks ]Median value of CD34+ in cells/kg collected from patients
- Analysis for Myc [ Time Frame: Up to 12 weeks ]Number of patients with mutant Myc regulatory gene
- Analysis for Bcl-2 [ Time Frame: Up to 12 weeks ]Number of patients with mutant B-cell lymphoma-2 genes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03064867
|Contact: Paolo Caimi, MD||1-800-641-2422||CTUReferral@UHhospitals.org|
|United States, Missouri|
|Washington University School of Medicine, Siteman Cancer Center||Suspended|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44106-5065|
|Contact: Paolo Caimi, MD 800-641-2422 CTUReferral@UHhospitals.org|
|Principal Investigator: Paolo Caimi, MD|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Brian Hill, MD 866-223-8100 TaussigResearch@ccf.org|
|Principal Investigator:||Paolo Caimi, MD||University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center|