Forecasting Relapse Outcomes With AlloHeme-based Risk Detection in Post-Allo-HCT AML/MDS Patients (FORWARD)

Official title

Forecasting Relapse Outcomes With AlloHeme-based Risk Detection in Post-Allo-HCT AML/MDS Patients (FORWARD): A Multicenter, Prospective Observational Cohort Study in US Transplant Centers

Overview

AlloHeme is a blood-based monitoring test developed by the CareDx laboratory that utilizes NGS technology coupled with a proprietary algorithm to predict the likelihood of a relapse in post-allo-HCT AML/MDS patients. The technology analyzes 405 single nucleotide polymorphisms (SNPs) selected from across all somatic chromosomes between the donor and the recipient. Pre-transplant DNA is obtained from donor and/or recipient to identify specific donor and recipient SNPs (baseline samples). Post-transplant blood samples are obtained and compared to the baseline sample profiles to precisely calculate the percentage chimerism of recipient cells in the blood samples using a proprietary quantitative method and unique dual indexing that optimizes recipient DNA at trace levels. This approach enables highly accurate and reproducible chimerism measurement with a limit of detection down to 0.02%. The AlloHeme test leverages a proprietary algorithm that integrates this multi-analyte longitudinal chimerism data with post-transplant time points to predict the likelihood of a clinical relapse for AML/MDS patients following an allo-HCT.

Interventions

• Diagnostic test AlloHeme
  AlloHeme is a blood-based monitoring test developed by the CareDx laboratory that utilizes NGS technology coupled with a proprietary algorithm to predict the likelihood of a relapse in post-allo-HCT AML/MDS patients. Measuring donor cells' DNA from the recipient's blood after stem cell transplant for some types of blood cancer may provide information on the likelihood of disease relapse in acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) disease populations. AlloHeme is a diagnosti

Primary outcome measures

• To evaluate AlloHeme test performance in predicting post-transplant relapse (by FDA criteria) or any cytogenetic/molecular evidence of disease resulting in unplanned treatment intervention in AML and MDS patients. [Time frame: 12 months]

Secondary outcome measures (5)

• The performance of the AlloHeme test in predicting post-transplant relapse as defined by the FDA in patients with AML and MDS will be evaluated using: o Sensitivity o Specificity o PPV o NPV o AuROC [Time frame: 12 months]
• The median lead time from a positive AlloHeme test result to a relapse in post-allo-HCT AML and MDS patients. [Time frame: 12 months]
• Hazard Ratio for relapse outcome. [Time frame: 12 months]
• The AlloHeme test performance in predicting post-transplant relapse will be compared with bone marrow MFC MRD and molecular MRD methods (NGS, qPCR, ddPCR)* in patients with AML and MDS using sensitivity, specificity, PPV, NPV, and AuROC measures. [Time frame: 12 months]
• The performance of the AlloHeme and peripheral blood-based STR-PCR tests in predicting post-transplant relapse in patients with AML and MDS will be evaluated using the following measures: o Sensitivity o Specificity o PPV o NPV o AuROC [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Adults aged 18 years or above.
• The participant must have one of the following diseases: AML or MDS (including CMML) and be eligible for allogeneic hematopoietic stem cell transplant. For participants with active disease (> 5% blasts) before HCT, the treating physician must have the intent to perform a bone marrow examination at day 30 post-HCT as SOC patient management to confirm complete remission (<5% blasts).
• Participant must receive an allo-HCT from an HLA-matched related or unrelated donor, an HLA-mismatched donor, or a haploidentical donor.
• Participant can be enrolled before, at, or up to 1-month post-allo-HCT as long as the participant is in complete remission (CR) at Day 30 and that a recipient pre-transplant or donor sample is available for baseline genotyping (reference). If the reference sample is unavailable or fails testing, the buccal swab collected at Day 30 may be used as the reference sample.
• Myeloablative or reduced intensity/non-myeloablative conditioning except T-cell depleting therapies (Ex-vivo T cell depletion, CD34 selected graft, use of anti-thymocyte globulin or alemtuzumab).
• Any graft versus host disease (GVHD) prophylaxis regimen.
• Willing and able to provide written informed consent.
• Willing and able to comply with study visits and procedures, including scheduled sample collections and clinical assessments

Exclusion criteria

• History of prior allo-HCT or any prior solid organ transplant.
• Syngeneic donor (identical twin).
• T cell depleted transplant (Ex-vivo T cell depletion, CD34 selected graft, use of antithymocyte globulin or alemtuzumab in the conditioning regimen)
• Cord blood graft.
• Pregnancy
• Any condition that, in the investigator's opinion, would interfere with the participant's ability to comply with study procedures or jeopardize their safety.
• Concurrent participation in an interventional or maintenance clinical trial for post allo-HCT relapse prevention; co-enrollment with other trials, such as those intended for GVHD / infection prevention or improving supportive care, is allowed.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• CareDx, Inc. — Brisbane

Identifiers

NCT: NCT07607327 · CDNACT2501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗