Defining ctDNA Metrics in Posttransplant Lymphoproliferative Disorder (PTLD)

NCT06954805 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: AAAV2404
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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

Keywords

posttransplant; lymphoproliferative disorder

Outcome Measures

Primary Outcomes (1)

• Number of participants with Complete Response (CR) rate of 60% or higher

  to determine the rate of early molecular response to induction rituximab as well as correlate the experience of undetectable measurable residual disease at mid-consolidation and end of treatment

  Up to 3 years

Secondary Outcomes (7)

• Circulating tumor DNA (ctDNA) rate

  Up to 3 years

• Event Free Survival rate

  Up to 3 years

• Duration of Overall Response (OR)

  Up to 3 years

• Duration of stable disease

  Up to 3 years

• Progression-Free Survival (PFS) rate

  Up to 3 years

Study Arms (2)

Arm A (Low-risk)

EXPERIMENTAL

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.

Drug: Rituximab; Device: CAPP-seq

Arm B (High-risk)

EXPERIMENTAL

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

Drug: Rituximab; Drug: Etoposide; Drug: Prednisone; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Doxorubicin; Device: CAPP-seq

Interventions

Rituximab DRUG

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.

Arm A (Low-risk); Arm B (High-risk)

Etoposide DRUG

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.

Also known as: Etopophos

Arm B (High-risk)

Prednisone DRUG

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.

Arm B (High-risk)

Vincristine DRUG

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.

Also known as: Oncovin

Arm B (High-risk)

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

Arm B (High-risk)

Doxorubicin DRUG

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.

Also known as: Adriamycin

Arm B (High-risk)

CAPP-seq DEVICE

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.

Also known as: cancer personalized profiling by deep sequencing, cell free DNA (cfDNA) assay

Arm A (Low-risk); Arm B (High-risk)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• Jennifer Amengual: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (2)

Stanford Medical Center

Stanford, California, 94305, United States

NOT YET RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell; Lymphoproliferative Disorders

Interventions

Rituximab; Etoposide; etoposide phosphate; Prednisone; Vincristine; Cyclophosphamide; Doxorubicin; Biological Assay

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Investigative Techniques

Study Officials

• Jennifer Amengual, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse Navigator

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: All participants will receive induction therapy consisting of 4 weekly cycles of rituximab. Following completion of induction therapy, participants will be risk stratified into one of two different consolidative treatment regimens based on whether they qualify as either low-risk or high-risk. Risk stratification will be made based on both radiographic response to induction therapy as well as the underlying biologic features of their PTLD.

Study Record Dates

• First Submitted: April 24, 2025
• First Posted: May 2, 2025
• Study Start: April 14, 2025
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): April 14, 2028
• Last Updated: May 2, 2025

Record last verified: 2025-04

Locations

US (2)