Rituximab + LMP-Specific T-Cells for Post-transplant Lymphoproliferative Disease

Recruiting at 38 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must be taking: Rituximab

Must not be taking: Anti-CD20 antibodies

Disqualifiers: CNS involvement, Bone marrow, Fulminant PTLD, Hepatitis, 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: 11

Duration: 6 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot phase II trial studies how well rituximab and latent membrane protein (LMP)-specific T-cells work in treating pediatric solid organ recipients with Epstein-Barr virus-positive, cluster of differentiation (CD)20-positive post-transplant lymphoproliferative disorder. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. LMP-specific T-cells are special immune system cells trained to recognize proteins found on post-transplant lymphoproliferative disorder tumor cells if they are infected with Epstein-Barr virus. Giving rituximab and LMP-specific T-cells may work better in treating pediatric organ recipients with post-transplant lymphoproliferative disorder than rituximab alone.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like myelosuppressive chemotherapy within 2 weeks, anti-CD20 monoclonal antibodies within 90 days, or investigational therapy within 30 days before joining the study.

What data supports the effectiveness of the treatment Rituximab + LMP-Specific T-Cells for Post-transplant Lymphoproliferative Disease?

Rituximab, a part of this treatment, has shown effectiveness in treating B-cell lymphomas, including post-transplant lymphoproliferative disorders, by achieving complete or partial remission in some patients. It is effective when used alone or with chemotherapy, and it has been used successfully in patients who have relapsed after other treatments. ^{1 2 3 4 5}

Is Rituximab safe for use in humans?

Rituximab has been used safely in various treatments, including for non-Hodgkin's lymphoma, where it was well tolerated by patients. Some patients experienced temporary low white blood cell counts, but overall, it is considered a safe treatment option. ^{1 2 6 7 8}

How is the treatment with Rituximab and LMP-specific T-cells for post-transplant lymphoproliferative disease different from other treatments?

This treatment is unique because it combines Rituximab, a monoclonal antibody targeting CD20 on B-cells, with LMP-specific T-cells that are designed to target and destroy cells infected with Epstein-Barr virus (EBV), which is often associated with post-transplant lymphoproliferative disease. This dual approach aims to enhance the immune system's ability to fight the disease more effectively than using Rituximab alone. ^{1 7 9 10 11}

Research Team

Birte Wistinghausen

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for pediatric patients who have had a solid organ transplant and are now facing EBV-positive, CD20-positive post-transplant lymphoproliferative disorder. They should not have received certain treatments like myelosuppressive chemotherapy or stem cell transplants recently, and must be in relatively good health with a life expectancy of at least 8 weeks.

Inclusion Criteria

My PTLD diagnosis is confirmed by biopsy and tests positive for CD20 and EBV.

My condition did not improve after reducing my immunosuppression medication by half or more for a week, or my doctor noted that reducing my medication could dangerously increase my risk of organ rejection.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

More than a quarter of my bone marrow is affected.

My CNS condition was confirmed with a spinal tap.

Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence of multi-organ involvement/failure including two or more of the following: Bone marrow (including pancytopenia without any detectable B-cell proliferation), Liver (coagulopathy, transaminitis and/or hyperbilirubinemia), Lungs (interstitial pneumonitis with or without pleural effusions), Gastrointestinal hemorrhage, Any documented donor-derived PTLD, Hepatitis B or C serologies consistent with past or current infections because of the risk of reactivation with rituximab, Severe and/or symptomatic refractory concurrent infection other than EBV, Pregnant females are ineligible since there is no available information regarding human fetal or teratogenic toxicities, Lactating females are not eligible unless they have agreed not to breastfeed their infants, Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained, Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 12 months following completion of study therapy., All patients and/or their parents or legal guardians must sign a written informed consent, All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive rituximab or biosimilar intravenously on days 1, 8, 15. Cycle continues for up to 21 days in the absence of disease progression or unacceptable toxicity.

3 weeks

3 visits (in-person)

Treatment

Patients receive allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes IV over 1-2 minutes on days 0 and 7. Cycle continues for up to 42 days in the absence of disease progression or unacceptable toxicity.

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

6 visits (in-person)

Treatment Details

Interventions

• Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes
• Rituximab

Trial Overview The trial is testing the effectiveness of Rituximab (a monoclonal antibody) combined with LMP-specific T-cells (immune cells trained to attack virus-infected tumor cells) against this type of lymphoproliferative disorder that occurs after an organ transplant.

Participant Groups

Group I: Arm II (LMP-TC) Experimental Treatment 2 Interventions

Patients with newly diagnosed PTLD who do not achieve a CR to induction, all relapsed patients after induction, and all patients with refractory disease who received rituximab or biosimilar within 90 days according to institutional guidelines, receive allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes IV over 1- 2 minutes on days 0 and 7. Cycle continues for up to 42 days in the absence of disease progression or unacceptable toxicity. Patients with PR or SD after first cycle of cycle allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes receive an additional cycle.

Group II: Arm I (RTX) Experimental Treatment 1 Intervention

Patients with newly diagnosed PTLD who achieve a complete response (CR) after induction receive additional rituximab or biosimilar as in induction.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 33 patients with aggressive non-Hodgkin's lymphoma, the combination of Rituxan (rituximab) and CHOP chemotherapy resulted in a high overall response rate of 94%, with 61% achieving a complete response.

The treatment was well-tolerated, with common side effects like fever and chills, and did not hinder the completion of the full six-course regimen, indicating both safety and efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. Vose, JM., Link, BK., Grossbard, ML., et al.[2022]

A 56-year-old man developed dilated cardiomyopathy after receiving rituximab and bendamustine for chronic lymphocytic leukemia, highlighting a potential serious cardiovascular side effect of rituximab.

Despite the adverse reaction, the patient fully recovered after treatment with medications for cardiomyopathy and supportive care, emphasizing the importance of monitoring for such effects in patients undergoing rituximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversible Cardiomyopathy after Rituximab Treatment in a Chronic Lymphocytic Leukemia Patient. Girkar, N., Zaki, S., Pawar, S., et al.[2022]

References

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

The role of the anti-CD20 antibody rituximab in hematopoietic stem cell transplantation for non-Hodgkin's lymphoma. [2015]

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

Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Treatment of post-transplant lymphoproliferative disease with induction chemotherapy followed by haploidentical peripheral blood stem cell transplantation and Rituximab. [2015]

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

Salvage therapy for relapsed posttransplant lymphoproliferative disorders (PTLD) with a second progression of PTLD after Upfront chemotherapy: the role of single-agent rituximab. [2021]

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

Role of chemotherapy and rituximab for treatment of posttransplant lymphoproliferative disorder in solid organ transplantation. [2015]

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

Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Rituximab in hematopoietic cell transplantation. [2015]

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

Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Reversible Cardiomyopathy after Rituximab Treatment in a Chronic Lymphocytic Leukemia Patient. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Rituximab: current status as therapy for malignant and benign hematologic disorders. [2016]

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

Outcome of Rituximab-Based Treatment for Post-Transplant Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience. [2020]