Venetoclax Plus R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03064867|
Recruitment Status : Suspended (Amendment pending to expand to Phase II)
First Posted : February 27, 2017
Last Update Posted : April 25, 2019
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: RICE||Phase 1|
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)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I 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|
|Actual Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||March 15, 2020|
Experimental: Venetoclax + RICE
Venetoclax with rituximab, ifosfamide, carboplatin, and etoposide
Beginning with 400mg daily on days 1-10 of cycle 1-3
rituximab, ifosfamide, carboplatin, etoposide on day 1-3 every 21 days
- 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 Patients Proceeding to Autologous Stem Cell Transplant [ Time Frame: Up to 12 weeks ]the number of patients with Autologous Stem Cell Transplant 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
|United States, Ohio|
|University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Paolo F Caimi, MD||University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|