PET Adapted Therapy for Non-Hodgkin's Lymphoma

Overseen By Robin Boerman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Pregnancy, Bulky disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for diffuse large B cell lymphoma (DLBCL), a type of non-Hodgkin's lymphoma. Researchers aim to determine if measuring a specific blood marker, circulating tumor DNA (ctDNA), can predict treatment effectiveness. Participants will receive a combination of drugs: Cyclophosphamide, Doxorubicin, Prednisone, Rituximab, and Vincristine. The trial seeks individuals who have not yet received treatment and have a specific form of DLBCL visible on certain scans. Candidates should have no serious uncontrolled health issues and must be able to undergo standard medical tests. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the R-CHOP treatment, a combination of five drugs, is generally effective for treating diffuse large B-cell lymphoma (DLBCL), curing about 70% of patients. However, some risks are involved. Studies have found that patients may experience heart problems, particularly heart failure, with this treatment. While the treatment is effective, these side effects are important to consider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment approach for Non-Hodgkin's Lymphoma because it adapts therapy based on PET scans, which could allow for more personalized treatment plans. This method uses the R-CHOP regimen, a combination of cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine, but adjusts the course of treatment based on early PET scan results. Unlike standard treatments that follow a fixed protocol, this approach aims to improve outcomes by tailoring therapy to the patient's specific response, potentially reducing unnecessary exposure to chemotherapy and enhancing effectiveness.

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

Research has shown that the R-CHOP treatment, a combination of five drugs, effectively treats diffuse large B cell lymphoma (DLBCL). Studies have found that this treatment cures about 70% of patients with DLBCL. In this trial, participants will receive the R-CHOP regimen, which includes rituximab, and studies have demonstrated that it significantly improves survival rates compared to CHOP alone. Specifically, after two years, 70% of patients treated with R-CHOP remained alive, highlighting its strong benefits. This combination is a well-established and proven approach for treating this type of lymphoma. ^{1 3 6 7 8}

Who Is on the Research Team?

Carla Casulo, MD

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for adults over 18 with early stage, non-bulky Diffuse Large B-Cell Lymphoma (DLBCL) who haven't been treated before. Participants need measurable disease visible on PET scans and available tumor biopsies. They must have good heart, kidney, liver function, stable blood counts, and no uncontrolled health issues or pregnancy.

Inclusion Criteria

All my other health conditions are under control.

My liver functions are within normal limits, or slightly elevated if I have Gilbert's disease.

My cancer can be seen and measured on a PET scan.

Exclusion Criteria

My cancer is larger than 10 cm in size.

Pregnancy, positive serum HCG within 28 days of enrollment, or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard chemoimmunotherapy and radiation based on the SWOG S1001 study

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of ctDNA at pre-defined time points

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Prednisone
• Rituximab
• Vincristine

Trial Overview The study tests how well patients respond to a combination of drugs: Vincristine, Prednisone, Rituximab Prednisone, Cyclophosphamide, Doxorubicin. It also monitors circulating tumor DNA levels in the body to potentially adapt treatment based on response.

How Is the Trial Designed?

Group I: Baseline PET Experimental Treatment 5 Interventions

R-CHOP

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

The combination of biweekly THP-COP chemotherapy and radiotherapy resulted in a high 5-year overall survival rate of 89% and a cause-specific survival rate of 90% in 41 patients with early-stage non-Hodgkin's lymphoma.

Despite some patients experiencing grade 4 neutropenia (12%), the treatment was well-tolerated, with 93% of patients completing the chemotherapy as scheduled, indicating that this regimen is both feasible and effective for low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Nishioka, T., Tsuchiya, K., Nishioka, S., et al.[2015]

In a study of 37 patients with relapsed/refractory aggressive lymphoma, the PACEBOM regimen demonstrated an overall response rate of 65% for Diffuse Large B-Cell Lymphoma (DLBCL), 70% for T-Cell Lymphoma (TCL), and 71% for Hodgkin lymphoma, indicating its efficacy as a treatment option.

The combination of PACEBOM with rituximab showed manageable toxicity, with the most common severe side effects being neutropenia (46%) and anemia (24%), suggesting that this treatment can be safely administered to patients previously treated with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. Tamjid, B., Mckendrick, J., Schwarer, A., et al.[2018]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

Current treatments for indolent non-Hodgkin's lymphoma, including watchful waiting and various chemotherapy regimens, have not achieved curative results, highlighting the need for innovative strategies.

Experimental approaches, such as increasing drug dose intensity, combining monoclonal antibodies with chemotherapy, and autologous stem-cell transplantation, are being explored as potentially more effective treatments, especially since less than 40% of patients with advanced aggressive non-Hodgkin's lymphoma are cured with standard chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current therapeutic paradigm for the treatment of non-Hodgkin's lymphoma. Fisher, RI.[2006]

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 401 patients with localized intermediate- and high-grade non-Hodgkin's lymphoma, three cycles of CHOP chemotherapy followed by involved-field radiotherapy significantly improved both progression-free survival (77% vs. 64%) and overall survival (82% vs. 72%) compared to eight cycles of CHOP alone.

The combination of CHOP and radiotherapy also showed a lower incidence of life-threatening toxic effects and no recorded cardiac events, suggesting a safer profile compared to CHOP alone, which had decreased left ventricular function in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. Miller, TP., Dahlberg, S., Cassady, JR., et al.[2022]

The CHASER chemoimmunotherapy regimen demonstrated a high overall response rate of 84% in 32 patients with relapsed or refractory B-cell non-Hodgkin's lymphoma, indicating its efficacy in treating this challenging condition.

The treatment was generally well tolerated, with manageable side effects, and allowed successful stem cell harvest in 19 out of 22 patients, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of a salvage regimen using cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Oki, Y., Ogura, M., Kato, H., et al.[2022]

A survey of 382 veterinarians revealed that 95% had diagnosed canine lymphoma in the past year, with 87% treating at least half of those cases, indicating a high prevalence of this condition in dogs.

The most commonly used treatment protocol for canine lymphoma was a combination of vincristine, cyclophosphamide, and prednisolone (COP), despite evidence suggesting that doxorubicin-based treatments may offer improved survival times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of canine lymphoma by veterinarians in first opinion practice in England. Mellanby, RJ., Herrtage, ME., Dobson, JM.[2019]

In a study of 23 patients with aggressive B-cell non-Hodgkin lymphoma, the combination of rituximab with CODOX-M/IVAC showed promising efficacy, with 83% of low-risk and 71% of high-risk patients achieving complete remission after treatment.

The safety profile was acceptable, with no treatment-related deaths and manageable toxicity, including only two cases of grade 3 neutropenia, suggesting that this treatment combination is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with CODOX-M/IVAC: a retrospective analysis of 23 cases of non-HIV related B-cell non-Hodgkin lymphoma with proliferation index >95%. Mohamedbhai, SG., Sibson, K., Marafioti, T., et al.[2015]

The study evaluated the cytotoxic effects of various anti-cancer drugs on canine lymphoma and leukemia cell lines, finding that vincristine (VINK) and doxorubicin (DOX) significantly reduced cell viability, while cyclophosphamide (CYC) induced the highest level of apoptosis.

Canine lymphoma and leukemia cell lines (CL-1, CLBL-1, GL-1) are effective models for testing new treatments, highlighting the potential for developing improved therapies for canine neoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of common antineoplastic agents on induction of apoptosis in canine lymphoma and leukemia cell lines. Pawlak, A., Rapak, A., Zbyryt, I., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7970687/

Rituximab in combination with cyclophosphamide ... R-CHOP cures approximately 70% of DLBCL patients. Dose-dense regimens do not show a benefit in response and increase toxicity.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa011795

CHOP Chemotherapy plus Rituximab Compared with ... Survival was significantly longer for patients treated with CHOP plus rituximab than for those treated with CHOP alone (P=0.007): at two years, 70 percent of ...

3. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext

Rituximab plus cyclophosphamide, doxorubicin, vincristine ... The primary endpoint of superior overall survival with R-CHOP-14 compared with R-CHOP-21 was not met, and R-CHOP-14 did not improve response ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/4964/Treatment-With-Four-Cycles-of-R-CHOP-Is-Non

Treatment With Four Cycles of R-CHOP Is Non-Inferior to Six ... At the end of therapy, 91% of patients in the 4-cycle group had a complete response or unconfirmed complete response, compared with 92% of patients in the 6- ...

5. eviq.org.au eviq.org.au/haematology-and-bmt/lymphoma/other-b-cell-lymphoma/70-r-chop21-rituximab-cyclophosphamide-doxorubici

70-R-CHOP21 (rituximab CYCLOPHOSPHamide ... BACKGROUND: Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20960528/

Activity and safety of dose-adjusted infusional ... The overall response rate was 90%, with a complete response rate of 57%. The 3-year overall survival and event-free survival rates were 56% and 54%, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302620300314

Articles Cardiovascular adverse events in patients with non ... Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high.

8. ashpublications.org ashpublications.org/blood/article/126/16/1893/34580/Frontline-rituximab-cyclophosphamide-doxorubicin

Frontline rituximab, cyclophosphamide, doxorubicin, and ... There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate ...