- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03583424
Venetoclax, Carmustine, Etoposide, Cytarabine, and Melphalan Before Stem Cell Transplant in Treating Participants With Relapsed or Refractory Non-Hodgkin Lymphoma
A Phase I/II Trial of Venetoclax and BEAM Conditioning Followed by Autologous Stem Cell Transplantation for Patients With Primary Refractory Non-Hodgkin Lymphoma
Study Overview
Status
Conditions
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Diffuse Large B-Cell Lymphoma
- Refractory Diffuse Large B-Cell Lymphoma
- Recurrent Non-Hodgkin Lymphoma
- Refractory Non-Hodgkin Lymphoma
- Hematopoietic Cell Transplantation Recipient
- Refractory Follicular Lymphoma
- Refractory Marginal Zone Lymphoma
- Refractory Transformed Indolent Non-Hodgkin Lymphoma
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / 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.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo hematopoietic cell transplantation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
At day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of progression
Time Frame: Up to 2 years
|
Estimated using Kaplan-Meier method.
|
Up to 2 years
|
Incidence of freedom from relapse
Time Frame: Up to 2 years
|
Estimated using Kaplan-Meier method.
|
Up to 2 years
|
Overall survival
Time Frame: Up to 2 years
|
Estimated using Kaplan-Meier method.
|
Up to 2 years
|
Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Recurrence
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell, Marginal Zone
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Keratolytic Agents
- Etoposide
- Etoposide phosphate
- Podophyllotoxin
- Venetoclax
- Melphalan
- Cytarabine
- Carmustine
- Mechlorethamine
- Nitrogen Mustard Compounds
Other Study ID Numbers
- OSU-17225
- NCI-2018-01039 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Grade 1 Follicular Lymphoma
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States, Canada, Singapore
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone... and other conditionsUnited States
-
Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsTerminatedFollicular Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular LymphomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Mantle Cell LymphomaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)WithdrawnRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Non-Hodgkin LymphomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Cutaneous B-cell Non-Hodgkin Lymphoma and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Recurrent Small Lymphocytic Lymphoma | Refractory Small Lymphocytic Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Refractory... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular... and other conditionsUnited States
-
National Cancer Institute (NCI)RecruitingRecurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
Clinical Trials on Etoposide
-
Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator...UnitedHealthcareActive, not recruitingSmall Cell Lung CancerUnited States
-
University Hospital, BonnCompletedEpendymomas | Recurrent Brain Tumors | Supratentorial PNETs | MedulloblastomasGermany
-
Sun Yat-sen UniversityRecruitingSmall Cell Lung CarcinomaChina
-
Guizhou Medical UniversityUnknownSmall-cell Lung CancerChina
-
Third Military Medical UniversityUnknownExtensive-stage Small Cell Lung Cancer
-
Jiangsu HengRui Medicine Co., Ltd.Enrolling by invitation
-
CephalonWithdrawn
-
Qingdao UniversityUnknownProgression Free SurvivalChina
-
Annick DesjardinsAstraZenecaCompletedGlioblastoma | GliosarcomaUnited States
-
Shanghai Henlius BiotechRecruitingExtensive Stage Small Cell Lung CancerUnited States