Rituximab + Stem Cell Transplant for Mantle Cell Lymphoma

Recruiting at 411 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Rituximab

Disqualifiers: CNS involvement, Pregnancy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

689 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it allows for up to two regimens of therapy, including conventional chemotherapy, antibody therapy, or an oral regimen, as long as a continuous response was ongoing throughout therapy.

What data supports the effectiveness of the treatment Rituximab + Stem Cell Transplant for Mantle Cell Lymphoma?

Research shows that adding rituximab to chemotherapy can significantly improve progression-free survival in mantle cell lymphoma patients. Additionally, rituximab maintenance therapy after autologous stem cell transplantation has been found to improve both progression-free and overall survival in these patients. ^{1 2 3 4 5}

Is the combination of Rituximab and Autologous Stem Cell Transplantation safe for treating Mantle Cell Lymphoma?

The combination of Rituximab and Autologous Stem Cell Transplantation can lead to significant side effects, including a high incidence of neutropenia (low white blood cell count) and thrombocytopenia (low platelet count), which can last several weeks. There is also a risk of secondary cancers, and some patients have experienced severe toxicity, which suggests careful consideration of risks is necessary. ^{1 2 4 6 7}

How is the Rituximab and Stem Cell Transplant treatment different for mantle cell lymphoma?

This treatment combines Rituximab, a drug that targets specific cancer cells, with a stem cell transplant to potentially improve outcomes for mantle cell lymphoma, a condition with no standard treatment. The unique aspect is the use of Rituximab as a consolidation therapy to clear remaining cancer cells after high-dose chemotherapy and stem cell transplant, which may enhance survival rates. ^{1 2 4 8 9}

What is the purpose of this trial?

This phase III trial studies rituximab after stem cell transplant and to see how well it works compared with rituximab alone in treating patients with in minimal residual disease-negative mantle cell lymphoma in first complete remission. Immunotherapy with rituximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving chemotherapy before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving rituximab with or without stem cell transplant may work better in treating patients with mantle cell lymphoma.

Research Team

Timothy S Fenske

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with mantle cell lymphoma in first complete remission and no minimal residual disease. Candidates must have completed certain therapies, be eligible for stem cell transplant, and not have CNS involvement by the lymphoma. HIV+ individuals can join if they meet specific health criteria. Pregnant or breastfeeding women are excluded, as well as those with recent other cancers or without a confirmed diagnosis.

Inclusion Criteria

Institution has received results from Adaptive Biotechnologies as defined by one of the following criteria

I have completed at least 4 cycles of initial cancer treatment.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Chemotherapy

Patients receive standard of care induction chemotherapy

6-8 weeks

Weekly visits (in-person)

Stem Cell Transplantation and Maintenance Rituximab

Patients undergo autologous hematopoietic stem cell transplantation followed by maintenance rituximab

18 cycles of rituximab every 8 weeks

Every 8 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 to 6 months (in-person)

Treatment Details

Interventions

• Autologous Hematopoietic Stem Cell Transplantation
• Rituximab

Trial Overview The study compares rituximab effectiveness after a stem cell transplant versus rituximab alone in treating mantle cell lymphoma that's in remission. It looks at how these treatments affect cancer cells' growth and spread, involving chemotherapy to prepare for the patient's own collected stem cells to be transplanted back into their body.

Participant Groups

Group I: Group II (rituximab) Experimental Treatment 7 Interventions

Patients receive standard of care induction chemotherapy. Beginning 40-180 days after completion of chemotherapy, patients receive rituximab or rituximab and hyaluronidase human or any approved rituximab biosimilar at the approved dose, as in Group I. Patients undergo PET, CT or PET/CT throughout the study. Patients may undergo blood sample collection during screening and on study. Patients also may undergo bone marrow biopsy and aspirate during screening.

Group II: Group I (auto-HCT, rituximab) Experimental Treatment 8 Interventions

Patients receive standard of care preparative chemotherapy and undergo auto-HCT. Beginning 100-140 days after transplant, patients receive rituximab IV or rituximab and hyaluronidase human SC or any approved rituximab biosimilar at the approved dose once every 8 weeks for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET, CT or PET/CT throughout the study. Patients may undergo blood sample collection during screening and on study. Patients also may undergo bone marrow biopsy and aspirate during screening.

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

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 14 patients with follicular or mantle-cell lymphoma, a high incidence of neutropenia was observed in those treated with rituximab before and after autologous stem cell transplantation (ASCT).

The findings highlight the potential safety concern of neutropenia associated with rituximab treatment in the context of high-dose therapy and stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation. Cairoli, R., Grillo, G., Tedeschi, A., et al.[2015]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

Rituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma. [2015]

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

Rituximab maintenance therapy for mantle cell lymphoma: A systematic review and meta-analysis. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group. [2021]

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

Phase 2 trial of rituximab plus hyper-CVAD alternating with rituximab plus methotrexate-cytarabine for relapsed or refractory aggressive mantle cell lymphoma. [2015]

6. Italy pubmed.ncbi.nlm.nih.gov

High incidence of neutropenia in patients treated with rituximab after autologous stem cell transplantation. [2015]

7. Croatia pubmed.ncbi.nlm.nih.gov

[Rituximab in the treatment of B-cell non-Hodgkin lymphoma]. [2015]

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

Clearing minimal residual disease with rituximab consolidation therapy. [2018]

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

Clearing Minimal Residual Disease with Rituximab Consolidation Therapy. [2019]