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

ConditionsAML (Acute Myelogenous Leukemia)MDS (Myelodysplastic Syndrome)CMML

Trial statusNot yet recruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorCareDx

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial population

AML, MDS, CMML

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

AlloHeme
Diagnostic test
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 diagnostic test that measures donor and recipient DNA in the recipient's blood. The purpose of this study is collecting blood samples from patients who have received a stem cell transplant in order to assess the ability of the AlloHeme test to predict clinical relapse. This approach enables highly accurate and reproducible chimerism measurement with a limit of detection down to 0.02%.

Treatment groups

No treatment groups listed

Trial outcomes

Primary outcomes

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.

The performance of AlloHeme test in predicting post-transplant relapse (by FDA criteria) or any cytogenetic/molecular evidence of disease resulting in unplanned treatment intervention (modified FDA criteria) in patients with AML and MDS will be evaluated using: * Sensitivity * Specificity * PPV * NPV * AuROC

Time frame

12 months

Secondary outcomes

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.

Lead time will be defined as the duration (in days) between the date of the first AlloHeme posi-tive result and the date of documented relapse.

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.

\*If either test yields a positive result, the overall assessment will be considered positive. For molecular MRD, a "positive" result must correspond to a known pathogenic variant judged by the treating physi-cian to be clinically relevant for relapse. MFC and/or molecular MRD performance will be based on transplant center-provided bone mar-row testing results.

Time frame

12 months

Other outcomes

The performance of the AlloHeme test in predicting post-transplant relapse will be described in subgroups of interest (AML vs MDS/CMML, conditioning regimen, risk assessment, etc.)

Performance will be evaluated using: * Sensitivity * Specificity * PPV * NPV * AuROC

Time frame

12 months

The performance of the AlloHeme test in predicting or detecting positive MRD as measured on bone marrow MFC MRD and/or molecular MRD testing modalities.

Performance will be evaluated using: * Sensitivity * Specificity * PPV * NPV * AuROC

Time frame

12 months

Relapse-free survival will be measured as the time interval from allo-HCT to the documented date of relapse or death from any cause and will be compared between the AlloHeme Positive and Negative groups.

Time frame

12 months

Sponsors and contacts

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CareDx

Lead sponsor

Source ClinicalTrials.gov

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