Rituximab, Venetoclax, and Bortezomib for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT04285268 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: 011915NCI-2020-00904P30CA072720
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well rituximab, venetoclax, and bortezomib work in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Venetoclax and bortezomib may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Giving rituximab, venetoclax, and bortezomib may slow or stop the growth of cancer cells in patients with diffuse large B-cell lymphoma.

Conditions

Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; High Grade B-Cell Lymphoma, Not Otherwise Specified; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Defined as the proportion of subjects who achieve a best response of a partial response (PR) or better. The ORR (complete and partial responses) will be reported as a percentage with a 95% confidence interval. If response is missing for any patients, those patients will still be included in the denominator when reporting the response rate.

  Up to 4 years

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 30 days post treatment

• Progression free survival (PFS)

  From study enrollment to disease progression or death from any cause, assessed up to 4 years

• Overall survival (OS)

  From study enrollment to the date of death from any cause, assessed up to 4 years

• Complete response (CR) and partial response (PR) rates

  Up to 4 years

• Duration of response (DoR)

  From when measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 4 years

Other Outcomes (1)

• BCL2 protein expression

  Up to 4 years

Study Arms (1)

Treatment (rituximab, venetoclax, bortezomib)

EXPERIMENTAL

Patients receive rituximab IV on day -1 of cycle 1, then on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 1-14 and bortezomib IV or SC on day -1 of cycle 1, then on days 1, 8, and 15 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles for rituximab and up to 26 cycles for venetoclax and bortezomib in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Biological: Rituximab; Drug: Venetoclax

Interventions

Bortezomib DRUG

Given IV or SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (rituximab, venetoclax, bortezomib)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (rituximab, venetoclax, bortezomib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (rituximab, venetoclax, bortezomib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed/refractory DLBCL defined as any of the following:
• Confirmed DLBCL/Burkitt lymphoma (BL)/B-cell lymphoma, unclassifiable (BCLU) by World Health Organization (WHO) 2016 classification
• Double hit lymphoma (DHL) phenotype as confirmed by FISH (fluorescent in-situ hybridization) or IHC (immunohistochemistry)
• Relapsed or progression of disease after at least one prior line of standard rituximab-cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone (R-CHOP), rituximab-etoposide-prednisone-oncovin-cyclophosphamide-hydroxydaunorubicin (R-EPOCH) or other R-CHOP-like therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• No prior treatment with a proteasome inhibitor or prior BCL2 inhibitor
• No cytotoxic chemotherapy within 2 weeks prior to study treatment
• Patients who are not candidates for salvage stem cell transplant or patients who are not candidates for CAR-T (chimeric antigen receptor T-cell) therapy, patients who have progressed or relapsed after a salvage transplant or CAR-T therapy are eligible
• Patients must give informed consent
• Prior radiation therapy allowed to \< 25% of the bone marrow and patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Patients treated with standard postoperative adjuvant radiation therapy for other cancers are allowed. Prior radiotherapy must be completed 14 days before study entry. Lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy
• Patients with lower blood counts due to marrow involvement by DHL will be eligible for the study
• Absolute neutrophil count (ANC) \>= 1,000/uL
• Platelets \>= 50,000/uL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 3 X institutional upper limit of normal (ULN)

You may not qualify if:

• Patients who have had prior proteasome inhibitor therapy or prior therapy with venetoclax
• Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
• Patients with history of hepatitis B with negative viral load are eligible (including latent carriers and patient with history of active disease who required treatment)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax and bortezomib or other agents used in the study
• Subjects with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) which is not well controlled on antiviral therapy
• Patients who have received autologous hematopoietic stem cell transplantation within 12 months
• Subject has received the following within 7 days prior to the first dose of study drug: Steroid therapy for anti-neoplastic intent, strong and moderate CYP3A inhibitors and/or strong and moderate CYP3A inducers
• The effects of combination venetoclax and bortezomib may cause fetal harm. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 12 weeks after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Bortezomib; Rituximab; CT-P10; venetoclax

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rajat Bannerji

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CINJ Regulatory - The PI is no longer affiliated with Rutgers

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: February 26, 2020
• Study Start: May 6, 2020
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (1)