New Cancer Treatment for Non-Hodgkin's Lymphoma

Recruiting at 3 trial locations

Overseen By Raul Ribeiro, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: HIV positive, Pregnant, Lactating, 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

128 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase III clinical trial using risk-adapted therapy. Treatment outcomes for children with B-cell NHL are excellent. Further improvements in outcome will likely be achieved through more focused study of the biology of the tumors and prospective studies of the late effects of treatment. Toward this end, this study features a spectrum of prospective biologic and late effect studies performed in patients treated with a modified regimen derived from the very successful LMB-96 regimen.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that participants have not been previously treated, except for limited use of steroids, one intrathecal chemotherapy treatment, or emergency radiation.

What data supports the effectiveness of the drug COP (Cyclophosphamide, Oncovin, and Prednisone) for treating non-Hodgkin's lymphoma?

The study comparing COP to another regimen (PmM) in patients with advanced low-grade non-Hodgkin's lymphoma showed that COP achieved an 83% overall response rate, indicating its effectiveness in treating this condition. ^{1 2 3 4 5}

What safety data exists for the COP treatment in humans?

The COP treatment, which includes cyclophosphamide, vincristine, and prednisone, has been studied for safety in patients with advanced low-grade non-Hodgkin's lymphoma. In a study comparing COP to another treatment, both had similar response rates, but COP was associated with some side effects, including hematologic toxicity (blood-related side effects) in a portion of patients. ^{1 2 4 5 6}

How is the COP treatment different from other drugs for non-Hodgkin's lymphoma?

The COP treatment, which includes cyclophosphamide, vincristine, and prednisone, is unique because it is often used in combination with other drugs or therapies to enhance its effectiveness, such as in the BCOP regimen for certain types of non-Hodgkin's lymphoma. This combination approach can lead to better outcomes in specific lymphoma subtypes compared to using COP alone. ^{1 2 3 4 7}

Research Team

Raul C. Ribeiro, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

This trial is for children and young adults under 22 years old with a diagnosis of mature B-cell lymphoma, such as Burkitt lymphoma or diffuse large B-cell lymphoma. They must be previously untreated or have had minimal treatment. Those with hepatitis B can participate but won't receive rituximab; HIV-positive patients are excluded from the therapy part but can join biology studies.

Inclusion Criteria

I have been diagnosed with a specific type of lymphoma (like Burkitt or large B-cell).

I have not received any treatment for my condition, except possibly a short course of steroids, one spinal chemotherapy session, or emergency radiation.

I was diagnosed before turning 22 years old.

Exclusion Criteria

Participants from collaborating sites participating in therapeutic and biological objectives must not meet the following criteria:

Participants known to be HIV positive (HIV participants are eligible for biology studies only).

Participants who are pregnant or lactating.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Phase

Participants receive COP as a pre-phase treatment

2 weeks

Induction

Participants receive COPAD M3 or COPADM8 cycles depending on group allocation

4-8 weeks

Consolidation

Participants receive CYM or CYVE cycles depending on group allocation

4 weeks

Maintenance

Participants in Group C receive maintenance therapy

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• COP
• COPAD
• COPADM8
• COPD M3
• CYM
• CYVE

Trial Overview The study tests modified treatments based on the LMB-96 regimen for various types of mature B-cell lymphomas in children. It's a phase III trial focusing on improving outcomes by studying tumor biology and long-term effects of these therapies.

Participant Groups

Group I: Group C Experimental Treatment 1 Intervention

Any CNS involvement and/or bone marrow involvement ≥ 25% blasts. For CNS involvement one or more of the following applies: 1. Any L3 blasts in CSF 2. Cranial nerve palsy (if not explained by extracranial tumor) 3. Clinical spinal cord compression 4. Isolated intracerebral mass 5. Parameningeal extension: cranial and/or spinal Group C will include the intervention COP, COPADM8, CYVE as follows: Pre-Phase: COP Induction: COPADM8 cycle 1 Induction: COPADM8 Cycle 2 Consolidation: CYVE x 2 cycles and Maintenance

Group II: Group B Experimental Treatment 1 Intervention

All cases not eligible for Group A or Group C. (Murphy Stage III and non-CNS Stage IV) Group B will include the intervention COP, COPD M3, CYM as follows: Pre-Phase: COP Induction: COPAD M3 x 2 cycles Consolidation: CYM x 2 cycles.

Group III: Group A Experimental Treatment 1 Intervention

Completely resected stage I or completely resected abdominal stage II lesions. Group A will include: COPAD x 2 cycles.

COP is already approved in United States, European Union for the following indications:

Approved in United States as COP for:

• Non-Hodgkin lymphoma
• Hodgkin lymphoma

Approved in European Union as COP for:

• Non-Hodgkin lymphoma
• Hodgkin lymphoma

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Findings from Research

The COAD-B chemotherapy regimen showed a 67.4% overall response rate in 86 patients with relapsed or refractory non-Hodgkin lymphoma, with a median remission duration of 13 months.

Patients who responded to COAD-B had better long-term survival rates, with 1-, 2-, and 4-year overall survival rates of 75.4%, 56.8%, and 40.0%, respectively, although the main adverse effect observed was myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of COAD-B regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma]. Li, MH., Li, YF., Yin, QS., et al.[2013]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Clinical study of COAD-B regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. German Low-Grade Lymphoma Study Group. [2015]

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

BCNU with and without cyclophosphamide, vincristine, and prednisone (COP) and cycle-active therapy in non-Hodgkin's lymphoma. [2015]

4. 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]

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

Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Exploring the burden of short-term CHOP chemotherapy adverse events in post-transplant lymphoproliferative disease: a comprehensive literature review in lymphoma patients. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Stage I and II non-Hodgkin's lymphoma: results of combined of THP-COP chemotherapy and radiotherapy. [2015]