Evaluating treatment options for posttransplant lymphoproliferative disorder

Defining the Role of ctDNA Monitoring in a Risk Stratified Clinical Trial for Posttransplant Lymphoproliferative Disorder (PTLD)

This study is testing a combination of rituximab and chemotherapy for patients with high-risk posttransplant lymphoproliferative disorder to see if it helps them better than just using rituximab alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 15 Years and up
• Sex: All
• Sponsor: Columbia University (Academic / other)
• Drugs / interventions: rituximab, chemotherapy, doxorubicin, cyclophosphamide, prednisone
• Locations: 2 sites (Stanford, California and 1 other locations)
• Trial ID: NCT06954805 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness of a combination treatment involving rituximab and R-EPOCH chemotherapy for patients with high-risk B-cell posttransplant lymphoproliferative disorder (PTLD). Participants with low-risk disease will receive rituximab alone to minimize chemotherapy exposure. Additionally, the study will investigate the role of circulating tumor DNA (ctDNA) as a potential tool for guiding treatment decisions and personalizing therapy. The trial is multi-center and open-label, focusing on improving treatment outcomes while reducing toxicity.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 15 and older with histologically confirmed CD20+ PTLD and measurable disease.

Not a fit: Patients with non-CD20+ PTLD or those with active Hepatitis B viral infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized and effective treatment strategies for patients with PTLD, potentially improving survival rates and reducing treatment-related side effects.

How similar studies have performed: Other studies have shown promise in using ctDNA for treatment guidance in various lymphomas, suggesting that this approach may be beneficial for PTLD as well.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed CD20+ PTLD including the below subtypes:

  * Polymorphic
  * Monomorphic
* Age ≥ 15.
* Participants must have measurable disease, defined as lymph node ≥ 1.5 cm in greatest diameter per Lugano Classification
* Patients must have a PET-CT scan (preferred; alternatively CT chest, abdomen and pelvis with IV contrast) performed within 28 days prior to the start of the study.
* All participants must be screened for chronic hepatitis B virus (HBV) within 28 days prior to registration. Participants with known HBV infection (positive serology) must also have a HBV viral load performed within 28 days prior to registration, and participants must have an undetectable HBV viral load on suppressive therapy within 28 days prior to start of treatment. Participants found to be HBV carriers during screening are eligible and must receive standard of care prophylaxis. Participants with active Hepatitis B (HBV viral load \> 500 IU/mL) within 28 days prior to registration are not eligible.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with an active HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration.
* Participants with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test (must be within 26 weeks prior to registration). Participants with known HIV must have a CD4 count checked within 28 days prior to registration, but may proceed with therapy regardless of CD4 count.
* Organ function as assessed by laboratory testing is in appropriate range for receipt of rituximab and R-EPOCH per individual treating physician discretion.
* Cardiac function testing is in appropriate range for receipt of rituximab and R-EPOCH per individual treating physician discretion.
* Eastern Cooperate Oncology Group (ECOG) performance status is in appropriate range for receipt of rituximab and R-EPOCH per individual treating physician discretion.
* Ability to understand and the willingness to sign a written informed consent document. In cases of partial impairment, impairment that fluctuates over time, or complete impairment due to dementia, stroke, traumatic brain injury, developmental disorders (including mentally disabled persons), serious mental illness, and delirium, a subject may be enrolled if the subject's legally authorized representative consents on the subject's behalf.
* Due to the potential teratogenic effects of chemotherapy, women of childbearing age must have a documented negative serum β-hCG measured within 2 weeks of starting treatment.
* Both women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).
* Women must agree to not breastfeed during the entirety of the study period.
* Participants must not have had chemotherapy for other indications within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier.
* Participants must not have received more than a cumulative of dose 250 mg/m 2 of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration).
* Intrathecal chemotherapy administered for CNS prophylaxis is allowed in addition to protocol therapy per institution practice.

Exclusion Criteria:

* Patients who have received systemic chemotherapy for PTLD.
* Patients who have known lymphomatous involvement of the central nervous system (CNS).

Where this trial is running

Stanford, California and 1 other locations

• Stanford Medical Center — Stanford, California, United States (Not_yet_recruiting)
• Columbia University Irving Medical Center — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jennifer Amengual, MD — Columbia University
• Study coordinator: Research Nurse Navigator

Conditions Lymphoma; Lymphoma, B-Cell; posttransplant; lymphoproliferative disorder