Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
18

Inclusion Criteria

Subjects must have the ability to understand and the willingness to sign a written informed consent document
Within 1 week prior to initiation of treatment: Calculated glomerular filtration rate (GFR) 30 ml/min
Karnofsky performance status >= 80%
...
Subjects must have the ability to understand and the willingness to sign a written informed consent document
Within 1 week prior to initiation of treatment: Calculated glomerular filtration rate (GFR) 30 ml/min
Karnofsky performance status >= 80%
Subjects must have histologically confirmed diagnosis of non-Hodgkin?s lymphoma that has relapsed, or is refractory, after upfront induction therapy. Excluded histologies are T-cell lymphomas, post-transplant lymphoproliferative disorder, Burkitt lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma. All other histologies are eligible that include but not limited to: diffuse-large B-cell lymphoma, follicular lymphoma (grades I, II, and III), marginal zone lymphoma, transformed indolent lymphoma, grey zone lymphoma, and undifferentiated B-cell lymphoma. Patients with non-Hodgkin's lymphoma (NHL) who are at high risk of relapse can be enrolled in sustained partial response (PR) after induction chemotherapy (PR1)
Patient must be otherwise eligible for autologous stem cell transplantation (ASCT) per local institutional guidelines
Ability to collect 2 x 10^6/kg CD34+ cells for transplantation
Within 1 week prior to initiation of treatment: Total bilirubin < 2 x ULN unless due to disease
Diffusion capacity of carbon monoxide (DLCO) >= 50% predicted
Within 1 week prior to initiation of treatment: Absolute neutrophil count (ANC) > 500 cells/mm^3
No serious disease, or condition, that, in the opinion of the investigator, would compromise the patient?s ability to participate in the study
Within 1 week prior to initiation of treatment: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limits of normal (ULN) unless due to disease
Within 1 week prior to initiation of treatment: Platelet count > 50 mm^3
Expected survival of more than six months
Left ventricular ejection fraction >= 40%

Exclusion Criteria

Patients with central nervous system (CNS) involved by lymphoma can be included if CNS disease is deemed controlled prior to enrollment as determined by the investigator. Patients with uncontrolled CNS disease will be excluded
Female patients who are pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male or female patients, who are sexually active and of the child bearing age, must be willing to practice accepted birth control measures
Subjects who sustained a complete metabolic response (CMR) by positron emission tomography (PET)-computed tomography (CT) (Deauville score of =< 3) after salvage chemotherapy unless lymphoma relapsed less than 12 months from the first day of last cycle of induction chemotherapy OR patient required more than 2 lines of salvage chemotherapy to sustain a CMR
...
Patients with central nervous system (CNS) involved by lymphoma can be included if CNS disease is deemed controlled prior to enrollment as determined by the investigator. Patients with uncontrolled CNS disease will be excluded
Female patients who are pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male or female patients, who are sexually active and of the child bearing age, must be willing to practice accepted birth control measures
Subjects who sustained a complete metabolic response (CMR) by positron emission tomography (PET)-computed tomography (CT) (Deauville score of =< 3) after salvage chemotherapy unless lymphoma relapsed less than 12 months from the first day of last cycle of induction chemotherapy OR patient required more than 2 lines of salvage chemotherapy to sustain a CMR
Patients who are human immunodeficiency virus (HIV) positive and receiving combination antiretroviral therapy will be excluded; because of the potential for pharmacokinetic interactions with venetoclax
Prior treatment with venetoclax
Subjects receiving any other investigational agents
Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or other agents used in this study

Summary

Conditions
  • Recurrent Marginal Zone Lymphoma
  • 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 Non-Hodgkin Lymphoma
  • Refractory Diffuse Large B Cell Lymphoma
  • Refractory Transformed Indolent Non-Hodgkin Lymphoma
  • Refractory Follicular Lymphoma
  • Refractory Marginal Zone Lymphoma
  • Refractory Non Hodgkin Lymphoma
Type
Interventional
Phase
Phase 1 & Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 19 years and 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: 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 ...

PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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.

Inclusion Criteria

Subjects must have the ability to understand and the willingness to sign a written informed consent document
Within 1 week prior to initiation of treatment: Calculated glomerular filtration rate (GFR) 30 ml/min
Karnofsky performance status >= 80%
...
Subjects must have the ability to understand and the willingness to sign a written informed consent document
Within 1 week prior to initiation of treatment: Calculated glomerular filtration rate (GFR) 30 ml/min
Karnofsky performance status >= 80%
Subjects must have histologically confirmed diagnosis of non-Hodgkin?s lymphoma that has relapsed, or is refractory, after upfront induction therapy. Excluded histologies are T-cell lymphomas, post-transplant lymphoproliferative disorder, Burkitt lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma. All other histologies are eligible that include but not limited to: diffuse-large B-cell lymphoma, follicular lymphoma (grades I, II, and III), marginal zone lymphoma, transformed indolent lymphoma, grey zone lymphoma, and undifferentiated B-cell lymphoma. Patients with non-Hodgkin's lymphoma (NHL) who are at high risk of relapse can be enrolled in sustained partial response (PR) after induction chemotherapy (PR1)
Patient must be otherwise eligible for autologous stem cell transplantation (ASCT) per local institutional guidelines
Ability to collect 2 x 10^6/kg CD34+ cells for transplantation
Within 1 week prior to initiation of treatment: Total bilirubin < 2 x ULN unless due to disease
Diffusion capacity of carbon monoxide (DLCO) >= 50% predicted
Within 1 week prior to initiation of treatment: Absolute neutrophil count (ANC) > 500 cells/mm^3
No serious disease, or condition, that, in the opinion of the investigator, would compromise the patient?s ability to participate in the study
Within 1 week prior to initiation of treatment: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limits of normal (ULN) unless due to disease
Within 1 week prior to initiation of treatment: Platelet count > 50 mm^3
Expected survival of more than six months
Left ventricular ejection fraction >= 40%

Exclusion Criteria

Patients with central nervous system (CNS) involved by lymphoma can be included if CNS disease is deemed controlled prior to enrollment as determined by the investigator. Patients with uncontrolled CNS disease will be excluded
Female patients who are pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male or female patients, who are sexually active and of the child bearing age, must be willing to practice accepted birth control measures
Subjects who sustained a complete metabolic response (CMR) by positron emission tomography (PET)-computed tomography (CT) (Deauville score of =< 3) after salvage chemotherapy unless lymphoma relapsed less than 12 months from the first day of last cycle of induction chemotherapy OR patient required more than 2 lines of salvage chemotherapy to sustain a CMR
...
Patients with central nervous system (CNS) involved by lymphoma can be included if CNS disease is deemed controlled prior to enrollment as determined by the investigator. Patients with uncontrolled CNS disease will be excluded
Female patients who are pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male or female patients, who are sexually active and of the child bearing age, must be willing to practice accepted birth control measures
Subjects who sustained a complete metabolic response (CMR) by positron emission tomography (PET)-computed tomography (CT) (Deauville score of =< 3) after salvage chemotherapy unless lymphoma relapsed less than 12 months from the first day of last cycle of induction chemotherapy OR patient required more than 2 lines of salvage chemotherapy to sustain a CMR
Patients who are human immunodeficiency virus (HIV) positive and receiving combination antiretroviral therapy will be excluded; because of the potential for pharmacokinetic interactions with venetoclax
Prior treatment with venetoclax
Subjects receiving any other investigational agents
Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or other agents used in this study

Locations

Columbus, Ohio, 43210
Columbus, Ohio, 43210

Tracking Information

NCT #
NCT03583424
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Basem William, MD Ohio State University Comprehensive Cancer Center
  • Basem William, MD Ohio State University Comprehensive Cancer Center