Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan Before Stem Cell Transplant in Treating Participants With Relapsed or Refractory Non-Hodgkin Lymphoma

NCT ID: NCT03583424

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-10
• Study Completion Date: 2021-09-30

Brief Summary

This phase I/II trial studies the side effects and best dose of venetoclax when given together with carmustine, etoposide, cytarabine, and melphalan before stem cell transplant in treating participants with non-Hodgkin lymphoma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as venetoclax, carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient?s bone marrow for new blood-forming cells (stem cells) to grow.

Detailed 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 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Carmustine

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo hematopoietic cell transplantation

Melphalan

Intervention Type: DRUG

Given IV

Venetoclax

Intervention Type: DRUG

Given PO

Interventions

Carmustine

Given IV

Intervention Type: DRUG

Cytarabine

Given IV

Intervention Type: DRUG

Etoposide

Given IV

Intervention Type: DRUG

Hematopoietic Cell Transplantation

Undergo hematopoietic cell transplantation

Intervention Type: PROCEDURE

Melphalan

Given IV

Intervention Type: DRUG

Venetoclax

Given PO

Intervention Type: DRUG

Other Intervention Names

BCNU; Becenum; Becenun; BiCNU; Bis(chloroethyl) Nitrosourea; Bis-Chloronitrosourea; Carmubris; Carmustin; Carmustinum; FDA 0345; Gliadel; N,N'-Bis(2-chloroethyl)-N-nitrosourea; Nitrourean; Nitrumon; SK 27702; SRI 1720; WR-139021; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; HCT; Hematopoietic Stem Cell Transplantation; HSCT; stem cell transplantation; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine nitrogen mustard; Sarcoclorin; Sarkolysin; WR-19813; ABT-0199; ABT-199; ABT199; GDC-0199; RG7601; Venclexta

Eligibility Criteria

Inclusion Criteria

• 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)
• Expected survival of more than six months
• Karnofsky performance status >= 80%
• 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: Total bilirubin < 2 x ULN unless due to disease
• Within 1 week prior to initiation of treatment: Calculated glomerular filtration rate (GFR) 30 ml/min
• Within 1 week prior to initiation of treatment: Absolute neutrophil count (ANC) > 500 cells/mm^3
• Within 1 week prior to initiation of treatment: Platelet count > 50 mm^3
• Left ventricular ejection fraction >= 40%
• Diffusion capacity of carbon monoxide (DLCO) >= 50% predicted
• Ability to collect 2 x 10^6/kg CD34+ cells for transplantation
• Patient must be otherwise eligible for autologous stem cell transplantation (ASCT) per local institutional guidelines
• No serious disease, or condition, that, in the opinion of the investigator, would compromise the patient?s ability to participate in the study
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• 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
• Subjects receiving any other investigational agents
• Prior treatment with venetoclax
• 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
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax or other agents used in this study
• 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
• 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
• 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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Kami Maddocks, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kami Maddocks, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://cancer.osu.edu

The Jamesline

Other Identifiers

NCI-2018-01039

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-17225

Identifier Type: -

Identifier Source: org_study_id