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

Ohio State University Comprehensive Cancer Center (Other)
Overall Status
Active, not recruiting ID

Study Details

Study Description

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

  1. 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).

  2. 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).

  1. Long term effects (progression-free survival [PFS] and overall survival [OS]) of addition of venetoclax to BEAM.

  2. 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 Design

Study Type:
Actual Enrollment :
19 participants
Intervention Model:
Single Group Assignment
None (Open Label)
Primary Purpose:
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 :
Sep 10, 2018
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
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.

Drug: Carmustine
Given IV
Other 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
  • Drug: Cytarabine
    Given IV
    Other Names:
  • .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
  • Drug: Etoposide
    Given IV
    Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
  • Procedure: Hematopoietic Cell Transplantation
    Undergo hematopoietic cell transplantation
    Other Names:
  • HCT
  • Hematopoietic Stem Cell Transplantation
  • HSCT
  • stem cell transplantation
  • Drug: Melphalan
    Given IV
    Other Names:
  • 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
  • Drug: Venetoclax
    Given PO
    Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta
  • Outcome Measures

    Primary Outcome Measures

    1. 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 [Up to 2 years]

    2. Overall response rate [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.

    Secondary Outcome Measures

    1. Incidence of progression [Up to 2 years]

      Estimated using Kaplan-Meier method.

    2. Incidence of freedom from relapse [Up to 2 years]

      Estimated using Kaplan-Meier method.

    3. Overall survival [Up to 2 years]

      Estimated using Kaplan-Meier method.

    Eligibility Criteria


    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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

    Contacts and Locations


    Site City State Country Postal Code
    1 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210

    Sponsors and Collaborators

    • Ohio State University Comprehensive Cancer Center


    • Principal Investigator: Kami Maddocks, MD, Ohio State University Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:


    None provided.
    Responsible Party:
    Kami Maddocks, Principal Investigator, Ohio State University Comprehensive Cancer Center Identifier:
    Other Study ID Numbers:
    • OSU-17225
    • NCI-2018-01039
    First Posted:
    Jul 11, 2018
    Last Update Posted:
    Oct 6, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 6, 2021