Defining ctDNA Metrics in Posttransplant Lymphoproliferative Disorder (PTLD)

Part of paid clinical trials in Stanford, California.

Sponsor
Jennifer Amengual
Study ID
NCT06954805
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
15 Years - N/A
Healthy Volunteers
Not accepted

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.
  • 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.

Study Details

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.

Key Dates

Start date
Apr 14, 2025
Status verified
May 2026
Primary completion
Apr 14, 2027
Completion
Apr 14, 2028

Study Design

Enrollment
30 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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
  • 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.

Primary Outcome Measure

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

Central Contacts

Locations (2)

FacilityCityStateZIPSite coordinators
Stanford Medical CenterStanfordCalifornia94305
Ash Alizadeh, MD, PhD
[email protected]
650-725-0120
Columbia University Irving Medical CenterNew YorkNew York10032
Research Nurse Navigator
[email protected]
212-342-5162
Jennifer Amengual, MD

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