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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the highest safe dose of a new drug combined with standard treatments for B-cell lymphoma, a type of blood cancer. Researchers are testing three different drug combinations, including Cisplatin (a chemotherapy drug), Dexamethasone (a corticosteroid), Gemcitabine (a chemotherapy drug), RiTUXimab Injection (an antibody therapy), Rituximab SC (a subcutaneous antibody therapy), and Venetoclax (a targeted therapy), to determine which works best without causing severe side effects. The study seeks participants previously diagnosed with aggressive B-cell lymphoma that has either returned or not responded to initial treatments.

As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have explored the safety of the treatments in this trial under various conditions. Tafasitamab, when combined with lenalidomide, was well-tolerated over five years in patients with diffuse large B-cell lymphoma (DLBCL), suggesting it might also be safe with R-GDP, which is part of this trial.

Glofitamab, another drug in the trial, was tested with similar medications and proved safe and manageable before stem cell transplants. Serious side effects, such as cytokine release syndrome (CRS), were rare, indicating a good safety profile.

Venetoclax, also included in the trial, was studied with R-ICE, a treatment similar to R-GDP, and showed promising safety results for patients with aggressive lymphomas.

While these findings are encouraging, it is important to note that this trial is in an early phase. Early-phase trials primarily focus on safety, so any new data will help confirm how well participants can tolerate these drug combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for B-cell lymphoma because they introduce new combinations and mechanisms of targeting cancer cells. Unlike traditional therapies that often include just chemotherapy and monoclonal antibodies, these novel combinations incorporate drugs like Tafasitamab and Glofitamab, which are designed to enhance the immune system's ability to attack cancer cells more effectively. Venetoclax, another key feature in one of the combinations, specifically targets the BCL-2 protein, which helps cancer cells survive. These innovative approaches could potentially improve treatment outcomes and offer new hope for patients with B-cell lymphoma.

What evidence suggests that this trial's treatments could be effective for B-Cell Lymphoma?

This trial will evaluate different combination therapies for B-cell lymphoma. Research has shown that Tafasitamab, one of the treatments in this trial, achieves a promising success rate of about 60% in patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL), including a complete recovery rate of around 40% when used with other treatments.

Glofitamab, another treatment option in this trial, is also effective. Studies have shown a success rate of 52% and a complete recovery rate of 39% in similar patients. Additionally, Glofitamab significantly reduces the risk of death, helping patients live longer.

For Venetoclax, which is also being studied in this trial, early studies combined with chemotherapy have shown potential benefits for aggressive B-cell lymphomas, although exact success rates are still under investigation.

Overall, these treatments offer hope for patients with challenging B-cell lymphomas. ^{2 6 7 8 9}

Who Is on the Research Team?

Tara Baetz

Principal Investigator

Cancer Centre of Southeastern Ontario at Kingston, ON, Canada

Sarit Assouline

Principal Investigator

The Jewish General Hospital, Montreal QC, Canada

Diego Villa

Principal Investigator

BCCA - Vancouver Cancer Centre, BC, Canada

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ... Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

2. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper198452.html

Paper: Glofitamab in Combination with Rituximab Plus ... In pts with R/R DLBCL treated with R-ICE prior to ASCT, the overall response rate (ORR) was 63.5% and complete response rate was 38.0% ( ...

3. ascopost.com ascopost.com/issues/august-25-2024/glofitamab-combination-therapy-shows-survival-benefit-in-relapsed-or-refractory-diffuse-large-b-cell-lymphoma/

Glofitamab Combination Therapy Shows Survival Benefit in ... The results showed a near doubling of median overall survival and a 38% reduction in the risk of death (hazard ratio [HR] = 0.62, P = .006).

4. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/bispecific-antibody-glofitamab-combination-with-chemoimmunotherapy-safe-and-effective-for-patients-with-relapsedrefractory-diffuse-large-b-cell-lymphoma-after-initial-therapy

Glofitamab and Chemoimmunotherapy Effective for R/R DLBCL A recent study demonstrates that combining glofitamab with salvage chemoimmunotherapy is safe and effective for patients with R/R DLBCL who ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/glofitamab-shows-staying-power-when-paired-with-r-chop-or-pola-r-chp-in-lbcl

Glofitamab Shows Staying Power When Paired With R- ... The ORR was 100, and the complete metabolic response was 98%. The 12-month PFS was 92% overall, 90% in arm A and 95% in arm B. The 12-month OS ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39661985/

Safety and efficacy of glofitamab for relapsed/refractory ... The median progression-free survival (PFS) was 3.6 months, whereas the median overall survival was 5.7 months. Notably, 13 patients (19%) were ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/hon.70096_812

812 | CANADIAN CANCER TRIALS GROUP LY.18: A ... Conclusions: Glofitamab in combination with R-GDP is safe and feasible prior to ASCT, with a low rate of CRS and expected rates of other ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04980222

NCT04980222 | A Study to Evaluate the Safety and ... This Phase II, open-label, multicenter study will evaluate the safety, efficacy, and pharmacokinetics of glofitamab in combination with rituximab in ...

9. haematologica.org haematologica.org/article/view/11929

New bispecific antibodies in diffuse large B-cell lymphoma Glofitamab (Glofit) plus R-CHOP has a favorable safety profile ... Feasibility and safety data of the chemotherapy-light combination of ...