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Defining ctDNA Metrics in Posttransplant Lymphoproliferative Disorder (PTLD)

ConditionsLymphomaLymphoma, B-Cell
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age15+
SponsorJennifer Amengual

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Polymorphic

Monomorphic

Age ≥ 15.

Participants must have measurable disease, defined as lymph node ≥ 1.5 cm in greatest diameter per Lugano Classification

Disqualifiers

Patients who have received systemic chemotherapy for PTLD.

Patients who have known lymphomatous involvement of the central nervous system (CNS).

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Arm A (Low-risk)Experimental treatment 2 interventions
Group B: Arm B (High-risk)Experimental treatment 7 interventions

Trial outcomes

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

Time frame
Up to 3 years

Secondary outcomes

1

Circulating tumor DNA (ctDNA) rate

to determine the rate of early molecular response to induction rituximab

Time frame
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).

Time frame
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).

Time frame
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.

Time frame
Up to 3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jennifer Amengual

Lead sponsor

Columbia University

Sponsor institution

The Leukemia and Lymphoma Society

Collaborator

Source ClinicalTrials.gov
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