Chemotherapy + Monoclonal Antibody Therapy for Non-Hodgkin's Lymphoma

Not currently recruiting at 263 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: SWOG Cancer Research Network

Must not be taking: Monoclonal antibodies

Disqualifiers: CNS involvement, Cardiac disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 206

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining chemotherapy with different monoclonal antibody treatments to determine the best option for non-Hodgkin's lymphoma. Monoclonal antibodies are special proteins that can directly target and attack cancer cells. Participants will receive one of two antibody treatments, Rituximab or Tositumomab, along with standard chemotherapy. Individuals diagnosed with certain stages of non-Hodgkin's lymphoma who have not yet received treatment may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in cancer treatment.

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 does allow prior use of prednisone for non-lymphoma related illnesses. 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?

Research has shown that combining CHOP chemotherapy with rituximab is generally safe. One study found that adding rituximab to CHOP reduced the risk of negative side effects by 42% compared to CHOP alone, allowing many patients to tolerate the treatment well.

Regarding tositumomab, studies indicate it is a safe and effective option, particularly for those with relapsed non-Hodgkin's lymphoma. Although some patients experienced serious side effects with CHOP, tositumomab itself has demonstrated positive results in treating the disease.

Both treatments in this trial have strong safety records. While some risks exist, they are typically manageable and expected in cancer treatments. It is important to consult a healthcare provider to determine if a trial is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Non-Hodgkin's Lymphoma because they combine traditional chemotherapy with innovative monoclonal antibody therapies. Unlike the standard CHOP regimen, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, the addition of rituximab in one arm targets the CD20 protein on B cells, potentially enhancing the immune system's ability to attack cancer cells. Another arm introduces tositumomab, combined with a radioactive iodine, which delivers targeted radiation directly to the cancer cells, possibly improving precision in treatment. These novel approaches could lead to more effective treatments with potentially fewer side effects by specifically targeting cancer cells.

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

Research has shown that adding rituximab to the CHOP chemotherapy treatment, one of the treatment arms in this trial, greatly improves outcomes for patients with non-Hodgkin's lymphoma. Studies have found that this combination reduces the risk of cancer-related issues by 42% compared to CHOP alone. Many patients treated with this combination experience long-term remission, making it a strong first-choice treatment option.

For another treatment arm in this trial, the CHOP plus tositumomab combination has also shown encouraging results. One study found that 57% of patients who did not fully respond to CHOP improved after adding tositumomab. Additionally, the time patients lived without their cancer worsening was significantly longer. Both treatments show promise in effectively managing non-Hodgkin's lymphoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Oliver W. Press, MD, PhD

Principal Investigator

Fred Hutchinson Cancer Center

Myron S. Czuczman, MD

Principal Investigator

Roswell Park Cancer Institute

Sandra J. Horning, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed, untreated stage II-IV follicular non-Hodgkin's lymphoma that tests positive for CD20 antigen. Participants must have good performance status, adequate blood counts, no severe heart issues or CNS involvement by lymphoma. They cannot be pregnant/nursing and must use effective contraception.

Inclusion Criteria

HIV negative

Not pregnant or nursing

Bidimensionally measurable disease

Exclusion Criteria

I have never received monoclonal antibody treatment for cancer.

Ejection fraction at least lower limit of normal by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram for questionable cardiac history

I have been diagnosed with congestive heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CHOP chemotherapy with or without rituximab or tositumomab for up to 6 courses

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Day 200, 1 year, every 6 months for 2 years, then annually

Long-term follow-up

Participants are monitored for progression-free and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Rituximab
• Tositumomab
• Vincristine

Trial Overview The study compares two monoclonal antibodies (rituximab and tositumomab) combined with chemotherapy drugs (cyclophosphamide, doxorubicin, prednisone, vincristine) in treating patients with non-Hodgkin's lymphoma. It aims to find out which antibody works better when paired with chemo.

How Is the Trial Designed?

Group I: Arm III (CHOP + tositumomab) Experimental Treatment 5 Interventions

Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.

Group II: Arm II (CHOP + rituximab) Experimental Treatment 5 Interventions

Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.

Group III: Arm I (CHOP only) Active Control 4 Interventions

Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1\. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)

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?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Eastern Cooperative Oncology Group

Collaborator

Trials

272

Recruited

153,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3286173/

Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and ... Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care.

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

CHOP Chemotherapy plus Rituximab Compared with ... According to the Cox analysis, the regimen of CHOP plus rituximab reduced the risk of events by 42 percent, as compared with the risk with CHOP alone (Table 2).

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

Rituximab plus cyclophosphamide, doxorubicin, vincristine ... Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in patients ...

4. 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 ... PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat indolent ...

5. ashpublications.org ashpublications.org/bloodadvances/article/5/4/984/475201/A-randomized-phase-2-3-study-of-R-CHOP-vs-CHOP

A randomized phase 2/3 study of R-CHOP vs CHOP ... The R-CHOP regimen that was administered every 3 weeks consisted of rituximab 375 mg/m2 on day 1, CPA 750 mg/m2, DXR 50 mg/m2, and vincristine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4694242/

Efficacy and safety of rituximab combined with ... The aim of this study is to systematically evaluate the safety and efficacy of rituximab plus CHOP (R-CHOP combined regimen) in patients with previously ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2013.54.6861

Extended Rituximab Exposure Time in the SMARTE-R ... Extended rituximab exposure compared with eight 2-week applications in combination with 6×R-CHOP-14 significantly improved outcome of elderly poor-prognosis ...