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LymphomaPhase 2NCT06954805

Defining ctDNA Metrics in Posttransplant Lymphoproliferative Disorder (PTLD)

A Phase 2 study testing Rituximab, Etoposide and Prednisone in people with Lymphoma and Lymphoma, B-Cell, run by Jennifer Amengual at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Lymphoma, Lymphoma, B-Cell
What is being tested?
Rituximab, Etoposide and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
14 Apr 2025to 14 Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
Show all 19Show fewer
  • 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.

Who cannot join

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

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites, 2 recruiting
  • Columbia University Irving Medical Center

    New York, New York, 10032

    Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Jennifer Amengual, MD

    Recruiting
  • Stanford Medical Center

    Stanford, California, 94305

    Ash Alizadeh, MD, PhD, 650-725-0120, arasha@stanford.edu

    Not yet recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

This is a multi-center, phase 2, open-label clinical trial to evaluate the efficacy of dose modified R-EPOCH in high-risk, treatment naïve CD20+ posttransplant lymphoproliferative disorder (PTLD) patients. The purpose of this study is to define the benefit of rituximab with etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) in patients who have high-risk B cell PTLD while those with low-risk disease will be spared of chemotherapy and treated with rituximab alone. Concurrently this study also seeks to evaluate the usefulness of circulating tumor DNA (ctDNA), a novel blood test which has been shown to improve a physician's ability to prognosticate and guide treatment decisions in other types of lymphoma. The goal is to demonstrate that ctDNA is a viable and informative tool in treating PTLD with the hope that in the future it may be used to individualize treatment for patients with PTLD in a way that limits treatment toxicity without losing the effectiveness of the treatment plan.

Keywords
posttransplant, lymphoproliferative disorder
Medical subject headings
Lymphoma, Lymphoma, B-Cell, Lymphoproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    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.

  • EtoposideDrug

    Also called Etopophos

    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.

  • PrednisoneDrug

    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.

  • VincristineDrug

    Also called Oncovin

    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.

  • CyclophosphamideDrug

    Also called Cytoxan

    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.

  • DoxorubicinDrug

    Also called Adriamycin

    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-seqDevice

    Also called cancer personalized profiling by deep sequencing, cell free DNA (cfDNA) assay

    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.

Study groups in NCT06954805
Study groupRoleWhat they receive
Arm A (Low-risk)ExperimentalFollowing 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.
Receives: Drug: Rituximab; Device: CAPP-seq
Arm B (High-risk)ExperimentalFollowing 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
Receives: Drug: Rituximab; Drug: Etoposide; Drug: Prednisone; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Doxorubicin; Device: CAPP-seq

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 3 years

Secondary outcomes (7)
  1. Circulating tumor DNA (ctDNA) rate

    to determine the rate of early molecular response to induction rituximab

    Measured: Up to 3 years

  2. Event Free Survival rate

    EFS is defined as the duration of time from start of treatment to the time of any treatment failure including disease progression, death, and treatment discontinuation for any reason (e.g., adverse effects or withdrawal).

    Measured: Up to 3 years

  3. Duration of Overall Response (OR)

    Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for Complete Response (CR) or Partial Response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Up to 3 years

  4. Duration of stable disease

    Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.

    Measured: Up to 3 years

  5. Progression-Free Survival (PFS) rate

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: Up to 3 years

  6. Early Molecular Response (EMR) rate

    EMR is defined as at least a 2-log fold reduction in circulating tumor DNA (ctDNA) levels between the start and completion of induction therapy.

    Measured: Up to 3 years

  7. Measurable Residual Disease (MRD) rate

    MRD refers to the quantity of ctDNA that can be detected at any given time point following the start of treatment. Undetectable MRD (uMRD) will refer to quantities of ctDNA that fall below the threshold of detection for the CAPP-Seq assay. MRD will be determined by ctDNA assay at both mid-consolidation (between cycles 6 and 7) and EOT (within 8 weeks of C8D1).

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 May 2025
  2. Study start14 Apr 2025
  3. Primary completion14 Apr 2027 (estimated)
  4. Study completion14 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06954805
Sponsor's protocol ID
AAAV2404
Status last verified
May 2026
First submitted
24 Apr 2025
Last updated
27 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab, Etoposide and Prednisone in people with Lymphoma and Lymphoma, B-Cell, run by Jennifer Amengual at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Research Nurse Navigator (212-342-5162, cancerclinicaltrials@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with Complete Response (CR) rate of 60% or higher (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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