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

Trial Summary

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.

What data supports the effectiveness of the drug combination used in PET Adapted Therapy for Non-Hodgkin's Lymphoma?

Research shows that adding rituximab to chemotherapy regimens like CODOX-M/IVAC can improve survival rates in certain types of lymphoma, including non-Hodgkin's lymphoma. Additionally, the combination of drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone has been effective in treating aggressive forms of lymphoma. ^{1 2 3 4 5}

Is PET Adapted Therapy for Non-Hodgkin's Lymphoma safe for humans?

The combination of rituximab with CODOX-M/IVAC chemotherapy, which includes drugs like cyclophosphamide, doxorubicin, and vincristine, has been studied in patients with non-Hodgkin's lymphoma and found to have a safety profile comparable to existing treatments, with no treatment-related deaths reported. Some patients experienced side effects like neutropenia (low white blood cell count), but these were manageable. Overall, the treatment was generally well tolerated in studies. ^{2 3 5 6 7}

What makes the PET Adapted Therapy for Non-Hodgkin's Lymphoma unique?

This treatment is unique because it uses PET scans to adapt the therapy based on the patient's response, combining drugs like rituximab with a chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) to potentially improve outcomes compared to standard treatments. ^{2 8 9 10 11}

What is the purpose of this trial?

The overarching goals of this study are to measure levels of circulating tumor DNA (ctDNA) in patients with early stage diffuse large B cell lymphoma (DLBCL), to assess the change in ctDNA during treatment in order to prospectively identify markers of treatment failure, and to use ctDNA as a future tool for response adapted therapy.

Research Team

Carla Casulo, MD

Principal Investigator

University of Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

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

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

2. England 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%. [2015]

3. England 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. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. [2018]

5. United States 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. [2015]

6. England 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. [2022]

7. 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]

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

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

9. Greece pubmed.ncbi.nlm.nih.gov

The effect of common antineoplastic agents on induction of apoptosis in canine lymphoma and leukemia cell lines. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Treatment of canine lymphoma by veterinarians in first opinion practice in England. [2019]

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

Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. [2022]