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

Recruiting in Palo Alto (17 mi)

+38 other locations

Overseen byBirte Wistinghausen

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Children's Oncology Group

No Placebo Group

Prior Safety Data

Breakthrough Therapy

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.

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.

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

Treatment Details

Interventions

Allogeneic LMP1/LMP2-Specific Cytotoxic T-Lymphocytes (CAR T-cell Therapy)
Rituximab (Monoclonal Antibodies)

Trial OverviewThe 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

2Treatment groups

Experimental Treatment

Group I: Arm II (LMP-TC)Experimental Treatment2 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 Treatment1 Intervention

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