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

Not currently recruiting at 40 trial locations
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Children's Oncology Group
Must be taking: Rituximab
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining rituximab and LMP-specific T-cells for children who have undergone organ transplants and now face post-transplant lymphoproliferative disorder (PTLD). Rituximab helps stop cancer cells from growing, while LMP-specific T-cells (allogeneic LMP1/LMP2-specific cytotoxic T-lymphocytes) are immune cells trained to attack virus-infected cancer cells. The trial will determine if this combination is more effective than rituximab alone. It is suitable for pediatric patients who have had a solid organ transplant and are dealing with this Epstein-Barr virus-related cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both rituximab and LMP-specific T-cells are generally safe for treating post-transplant lymphoproliferative disorder (PTLD). Rituximab, a monoclonal antibody, has proven safe and effective for PTLD, especially following stem cell transplants. Studies indicate it can be administered without major side effects when given in recommended doses.

LMP-specific T-cells are immune cells that target the Epstein-Barr virus, often linked to PTLD. Research shows these cells are usually safe and well-tolerated. Studies have found they do not cause severe reactions like cytokine release syndrome or acute graft-versus-host disease, which can be serious with other treatments.

Both rituximab and LMP-specific T-cells have undergone thorough safety studies. Participants in these studies generally tolerated the treatments well, with few reports of serious side effects. This suggests they could be a safe option for those eligible for clinical trials for PTLD.12345

Why are researchers excited about this trial's treatments?

Unlike the standard of care for post-transplant lymphoproliferative disease, which typically involves medications like rituximab that target specific proteins on B-cells, this new approach incorporates LMP-specific cytotoxic T-lymphocytes. These T-cells are engineered to target the LMP1 and LMP2 proteins, which are associated with certain virus-driven cancers. Researchers are excited about this treatment because it leverages the body’s immune system to target cancer cells more precisely. This precision could mean fewer side effects and a more powerful attack on the disease itself, especially for those who don't fully respond to traditional treatments.

What evidence suggests that rituximab and LMP-specific T-cells might be an effective treatment for post-transplant lymphoproliferative disorder?

Research has shown that rituximab, one of the treatments in this trial, effectively treats post-transplant lymphoproliferative disorder (PTLD). Studies have found that patients receiving rituximab often experience significant improvement, with some achieving a complete response, meaning their symptoms can fully disappear. In this trial, some participants will receive rituximab alone.

Another treatment arm involves LMP-specific T-cells, a type of immune cell trained to target certain proteins. These cells have shown promise in helping the body fight PTLD, especially when linked to the Epstein-Barr virus. Combining rituximab with LMP-specific T-cells is believed to be more effective than using rituximab alone for treating PTLD in children. Early findings suggest this combination can better address the disorder by leveraging the strengths of both treatments.13456

Who Is on the Research Team?

BW

Birte Wistinghausen

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.
See 14 more

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
See 1 more

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm II (LMP-TC)Experimental Treatment2 Interventions
Group II: Arm I (RTX)Experimental Treatment1 Intervention

Find a Clinic Near You

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+

Published Research Related to This Trial

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

Citations

Recent Advances in Adult Post-Transplant ... - PubMed CentralPTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence.
Rituximab and LMP-Specific T-Cells in Treating Pediatric ...Giving rituximab and LMP-specific T-cells may work better in treating pediatric organ recipients with post-transplant lymphoproliferative disorder than ...
Long-Term Efficacy of Epstein-Barr Virus-Specific T Cells ...Adoptive transfer of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) offers a promising strategy to restore antiviral immunity, but long-term ...
Outcomes following posttransplant virus-specific T-cell therapy ...Outcomes following posttransplant virus-specific T-cell therapy in patients with sickle cell disease. Available Clinical Trials & Observations.
T-Cell Posttransplant Lymphoproliferative Disorders After ...Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell ...
EBV/LMP-specific T cells maintain remissions of THence, this study shows that donor-derived LMP-Ts are a safe and effective therapy to prevent relapse after transplantation in patients with B cell– or T cell– ...
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