Recruiting
Phase 2

R-EPOCH & Rituximab

Sponsor:

Jennifer Amengual

Code:

NCT06954805

Conditions

Lymphoma

Lymphoma, B-Cell

Eligibility Criteria

Sex: All

Age: 15+

Healthy Volunteers: Not accepted

Interventions

Rituximab

Etoposide

Prednisone

Vincristine

Cyclophosphamide

Study Details

Brief summary:

The purpose of this study is to find out if there is a benefit to giving rituximab with etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) in participants who have high-risk B-cell PTLD in their 2nd phase of treatment (consolidation) while those with low-risk disease will be spared of chemotherapy and treated with rituximab consolidation alone.

This study is also being done to find out about the usefulness of circulating tumor DNA (ctDNA), a novel blood test which, has been shown to help guide treatment decisions in other types of lymphoma. The goal is to answer the question if ctDNA is a viable and informative tool in treating PTLD with the hope that in the future it may be used to individualize study treatment for participants with PTLD in a way that limits study treatment toxicity without losing the effectiveness of the treatment plan.

Conditions

Lymphoma

Lymphoma, B-Cell

Study ID

NCT06954805

Start date

Apr 14, 2025

Status verified date

May, 2026

Completion date

Apr 14, 2028

Anticipated

Primary completion date

Apr 14, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 15+

Healthy Volunteers: Not accepted

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).

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (Low-risk)

Following completion of induction therapy, participants will be assigned to Arm A if they meet the following criteria:

1. Complete response to rituximab induction

OR
2. Partial response to rituximab induction without any additional high-risk features.

Low-risk participants will receive IV rituximab 375 mg/m2 every 21 days for 4 cycles.

experimental: Arm B (High-risk)

Following completion of induction therapy, participants will be assigned to Arm B if they meet the following criteria:

1. Stable disease
2. Progressive disease

OR
3. Partial response to rituximab induction with any of the following:

  • Residual bulky disease, defined as any single lesion measuring ≥ 7 cm or any 3 lesions each measuring ≥ 3 cm
  • High risk cytogenetic features including a complex karyotype (defined as ≥3 abnormalities on conventional karyotype), FISH positive for MYC rearrangement, double hit lymphoma (defined as MYC rearranged with BCL2 or BCL6), or p53 derangements
  • Plasmablastoid histology

High-risk participants will receive R-EPOCH every 21 days for 4 cycles:

  • Rituximab 375 mg/m2 IV Day 1
  • Etoposide 50 mg/m2 IV Day 1, 2, 3, 4
  • Prednisone 60 mg/m2 PO Day 1, 2, 3, 4, 5
  • Vincristine 0.4 mg/m2 IV Day 1, 2, 3, 4
  • Cyclophosphamide 375 mg/m2 IV Day 5
  • Doxorubicin 10 mg/m2 IV Day 1, 2, 3, 4

Interventions

Rituximab

Rituximab is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. The Fab domain of rituximab binds to the CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to mediate B cell lysis. 375 mg/m2 Rituximab will be administered to participants by IV.

Etoposide

Etoposide is a topoisomerase II inhibitor and appears to cause DNA strand breaks. It has been shown to delay transit of cells through S phase and arrest cells in late S or early G2 phase. 50 mg/m2 Etoposide will be administered to participants by IV.

Prednisone

Prednisone can prevent or suppress inflammation and immune responses. Prednisone's action may include the inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. 60 mg/m2 Prednisone will be administered to participants by PO.

Vincristine

Vincristine is a vinca alkaloid. The mechanism of action of vincristine is thought to be due to inhibition of microtubule formation in the mitotic spindle. This leads to arrest of dividing cells during the metaphase stage. 0.4 mg/m2 Vincristine will be administered to participants by IV.

Cyclophosphamide

The mechanism of action is thought to involve cross-linking of tumor cell DNA. Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites which are thought to cross-link to tumor cell DNA. These metabolites interfere with the growth of rapidly proliferating susceptible malignant cells. 375 mg/m2 Cyclophosphamide will be administered to participants by IV.

Doxorubicin

Doxorubicin is an anthracycline, topoisomerase II inhibitor. It is isolated from cultures of Streptomyces peucetius var. caesius. The cytotoxic effect of doxorubicin is related to nucleotide base intercalation and cell membrane lipid binding activities. It blocks nucleotide replication and the action of DNA and RNA polymerases. The interaction between doxorubicin and topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of its cytocidal activity. 10 mg/m2 Doxorubicin will be administered to participants by IV.

CAPP-seq

Next generation sequencing (NGS) tool used to detect tiny amounts of cancer DNA in the blood, allowing for early diagnosis and monitoring of cancer in a non-invasive way.

Primary outcome measure

  • Number of participants with Complete Response (CR) rate of 60% or higher [ Time Frame: Up to 3 years ]

Central Contacts and Locations

Central contacts

Research Nurse Navigator

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Locations

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

Research Nurse Navigator

212-342-5162cancerclinicaltrials@cumc.columbia.edu

More Information

Sponsor

Jennifer Amengual

Last update posted

May 27, 2026

Last verified

May, 2026

Keywords

  • posttransplant
  • lymphoproliferative disorder

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Jennifer Amengual on 2026-05-27.