Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan Before Stem Cell Transplant in Treating Participants With Relapsed or Refractory Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT03583424|
Recruitment Status : Active, not recruiting
First Posted : July 11, 2018
Last Update Posted : September 16, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hematopoietic Cell Transplantation Recipient Recurrent Diffuse Large B-Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory Marginal Zone Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Transformed Indolent Non-Hodgkin Lymphoma||Drug: Carmustine Drug: Cytarabine Drug: Etoposide Procedure: Hematopoietic Cell Transplantation Drug: Melphalan Drug: Venetoclax||Phase 1 Phase 2|
I. Determine the maximum tolerated dose (MTD) of venetoclax that can be safely combined with carmustine, etoposide, cytarabine, and melphalan (BEAM) prior to autologous stem cell transplant which will the recommended phase II dose (RP2D).
II. Determine the safety and efficacy of venetoclax as measured by overall response rate (ORR) at day 100, 12-month survival and freedom from relapse (FFR-12).
I. Long term effects (progression-free survival [PFS] and overall survival [OS]) of addition of venetoclax to BEAM.
II. Correlation of response and survival with expression of BCL-2, BCL-XL, and MCL-1 as measured by immunohistochemistry (IHC).
OUTLINE: This is a dose-escalation study of venetoclax.
Participants receive venetoclax orally (PO) once daily (QD) on days -10 to -1, carmustine intravenously (IV) on day -6, etoposide IV twice daily (BID) on days -5 to -2, cytarabine IV BID on days -5 to -2, and melphalan IV on day -1. Participants then undergo hematopoietic stem cell transplantation on day 0.
After completion of study treatment, participants are followed up for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial of Venetoclax and BEAM Conditioning Followed by Autologous Stem Cell Transplantation for Patients With Primary Refractory Non-Hodgkin Lymphoma|
|Actual Study Start Date :||July 9, 2018|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (venetoclax, BEAM)
Participants receive venetoclax PO QD on days -10 to -1, carmustine IV on day -6, etoposide IV BID on days -5 to -2, cytarabine IV BID on days -5 to -2, and melphalan IV on day -1. Participants then undergo hematopoietic cell transplantation on day 0.
Procedure: Hematopoietic Cell Transplantation
Undergo hematopoietic cell transplantation
- Maximum tolerated dose of venetoclax defined to be the dose cohort below which 3 out of 6 patients experience dose limiting toxicities or the highest dose cohort of 1200 mg, if 2 dose limiting toxicities are not observed at any dose cohort [ Time Frame: Up to 2 years ]
- Overall response rate [ Time Frame: At day 100 ]Will be estimated as the proportions of patients who achieve a complete response or partial response divided by the number of evaluable patients. Each will be reported with their associated 95% confidence interval.
- Incidence of progression [ Time Frame: Up to 2 years ]Estimated using Kaplan-Meier method.
- Incidence of freedom from relapse [ Time Frame: Up to 2 years ]Estimated using Kaplan-Meier method.
- Overall survival [ Time Frame: Up to 2 years ]Estimated using Kaplan-Meier method.
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): NCT03583424
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Basem William, MD||Ohio State University Comprehensive Cancer Center|