Novel Combination Therapy for B-Cell Lymphoma

Recruiting at 4 trial locations

Overseen By Lois Shepherd

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: Canadian Cancer Trials Group

Must not be taking: Cytotoxics, Biologics, Steroids, Radiation

Disqualifiers: HIV, Hepatitis, Cardiac conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like biologic agents and radiation are not allowed within 28 days before enrollment, and steroids should be avoided 7 days prior unless necessary. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination therapy for B-cell lymphoma?

Rituximab, a key component of the combination therapy, has been shown to significantly improve outcomes in B-cell lymphomas like diffuse large B-cell lymphoma and follicular lymphoma when added to chemotherapy. Studies have demonstrated that rituximab enhances response rates, progression-free survival, and overall survival in these conditions. ^{1 2 3 4 5}

Is the novel combination therapy for B-cell lymphoma safe for humans?

The combination therapy involving Venetoclax and Rituximab has been shown to have a manageable safety profile in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Common side effects include blood-related issues like neutropenia (low white blood cell count), but these are generally manageable with proper care. ^{6 7 8 9 10}

What makes the novel combination therapy for B-cell lymphoma unique?

This novel combination therapy for B-cell lymphoma is unique because it combines multiple drugs, including rituximab and venetoclax, which target cancer cells in different ways. Rituximab is a monoclonal antibody that targets the CD20 protein on B-cells, while venetoclax helps induce cancer cell death by inhibiting a protein called BCL-2. This multi-faceted approach may enhance treatment effectiveness compared to standard therapies. ^{5 11 12 13 14}

What is the purpose of this trial?

The purpose of this study is to find the highest dose of a new drug, in combination with standard drugs, which can be tolerated without causing very severe side effects. The study treatment is new agents in combination with R-GDP or an equivalent regimen.

Research Team

Sarit Assouline

Principal Investigator

The Jewish General Hospital, Montreal QC, Canada

Diego Villa

Principal Investigator

BCCA - Vancouver Cancer Centre, BC, Canada

Tara Baetz

Principal Investigator

Cancer Centre of Southeastern Ontario at Kingston, ON, Canada

Eligibility Criteria

This trial is for adults under 65 with aggressive B-cell lymphoma that's come back or didn't respond to first treatments. They must be fit enough for intensive chemo and a stem cell transplant, have measurable disease, and not have severe heart issues, uncontrolled infections, or other cancers being treated. Women who can get pregnant and men must agree to contraception.

Inclusion Criteria

I have been diagnosed with a specific type of lymphoma or my previous lymphoma has transformed into a more aggressive form.

In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient enrollment.

AST and ALT ≤ 3x ULN

Exclusion Criteria

I have had a serious stomach or intestinal bleed in the last month.

I have not received any live vaccines in the last 4 weeks.

I have not started any new treatments in the last two weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive increasing doses of the new drug in combination with R-GDP to determine the highest tolerable dose without severe side effects

8-12 weeks

Treatment

Participants receive the new drug in combination with R-GDP at the determined dose

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cisplatin
• Dexamethasone
• Gemcitabine
• RiTUXimab Injection
• Rituximab SC
• Venetoclax

Trial Overview The study tests new drug combinations alongside standard R-GDP chemotherapy (Rituximab, Gemcitabine, Dexamethasone, Cisplatin) or similar regimens in patients whose lymphoma has returned or resisted treatment. It aims to find the highest safe dose of these new combos without causing very severe side effects.

Participant Groups

Group I: Venetoclax + R-GDP Experimental Treatment 6 Interventions

Group II: Tafasitamab + R-GDP Experimental Treatment 1 Intervention

Group III: Glofitamab + R-GDP Experimental Treatment 6 Interventions

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

The addition of rituximab, a monoclonal antibody, to conventional chemotherapy (R-CHOP regimen) significantly enhances treatment outcomes for patients with diffuse large B-cell lymphoma (DLBCL), improving response rates, progression-free survival (PFS), and overall survival (OS).

Rituximab also boosts response rates and PFS in mantle cell lymphoma (MCL) and improves outcomes in follicular lymphoma (FL), highlighting its critical role in enhancing the efficacy of chemotherapy across various types of non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. Kahl, B.[2021]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

In a phase 1/2 study involving 12 Japanese patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), venetoclax demonstrated a 100% objective response rate (ORR) in patients receiving monotherapy, with a complete remission (CR) rate of 17%.

When combined with rituximab, venetoclax achieved a 67% ORR and a 50% CR rate, indicating that both treatment strategies are effective and well-tolerated, with a safety profile consistent with previous studies in Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of venetoclax, a BCL-2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. Izutsu, K., Yamamoto, K., Kato, K., et al.[2021]

Venetoclax is an effective oral medication for treating chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), showing significant efficacy when combined with other therapies like obinutuzumab and azacitidine.

While venetoclax is associated with adverse events such as neutropenia and gastrointestinal disorders, the article emphasizes the importance of managing these side effects to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. Waggoner, M., Katsetos, J., Thomas, E., et al.[2022]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

In a study of 32 patients with indolent B-cell non-Hodgkin lymphoma, the combination treatment of cyclophosphamide, mitoxantrone, and rituximab (CyMiR) achieved a high overall response rate of 90%, with 23 patients reaching complete remission.

The treatment was well tolerated, with only 10% of patients experiencing mild infusion-related toxicity from rituximab, indicating that this regimen effectively balances efficacy with quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone-cyclophosphamide-rituximab: an effective and safe combination for indolent NHL. Emmanouilides, C., Territo, M., Menco, H., et al.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

In a study of 38 patients with aggressive lymphomas, the combination of rituximab (a monoclonal antibody) with chemotherapy resulted in complete remission rates of 85% for untreated patients and 64% for those with relapsed or refractory disease, indicating high efficacy.

At a median follow-up of 12 months, the progression-free survival rate was 85% and overall survival was 79% in untreated patients, suggesting that rituximab enhances the effectiveness of chemotherapy in treating B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of rituximab and chemotherapy in aggressive B-cell lymphoma: A preliminary report of dose-adjusted EPOCH-R. Wilson, WH., Gutierrez, M., O'Connor, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy combinations with monoclonal antibodies in non-Hodgkin's lymphoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

7. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

8. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of venetoclax, a BCL-2 inhibitor, in Japanese patients with relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Mitoxantrone-cyclophosphamide-rituximab: an effective and safe combination for indolent NHL. [2015]

13. United States pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

The role of rituximab and chemotherapy in aggressive B-cell lymphoma: A preliminary report of dose-adjusted EPOCH-R. [2022]