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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: MDS (Myelodysplastic Syndrome); CMML; AML (Acute Myelogenous Leukemia)
• Intervention / Treatment: Diagnostic test: AlloHeme

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Nishant Dwivedi, MD, PhD; Phone Number: 508-981-6087; Email: ndwivedi@caredx.com

Study Locations

• United States
  • California
    • Brisbane, California, United States, 94080
      • CareDx, Inc.
      • Contact: Nishant Dwivedi, MD, PhD; Phone Number: 508-981-6087; Email: ndwivedi@caredx.com
      • Contact: Nishant Dwivedi, MD, PhD; Email: ndwivedi@caredx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

AML, MDS, CMML

Description

Inclusion Criteria:

1. Adults aged 18 years or above.
2. 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).
3. Participant must receive an allo-HCT from an HLA-matched related or unrelated donor, an HLA-mismatched donor, or a haploidentical donor.
4. 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.
5. 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).
6. Any graft versus host disease (GVHD) prophylaxis regimen.
7. Willing and able to provide written informed consent.
8. Willing and able to comply with study visits and procedures, including scheduled sample collections and clinical assessments

Exclusion Criteria:

1. History of prior allo-HCT or any prior solid organ transplant.
2. Syngeneic donor (identical twin).
3. T cell depleted transplant (Ex-vivo T cell depletion, CD34 selected graft, use of antithymocyte globulin or alemtuzumab in the conditioning regimen)
4. Cord blood graft.
5. Pregnancy
6. Any condition that, in the investigator's opinion, would interfere with the participant's ability to comply with study procedures or jeopardize their safety.
7. 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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		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.	12 months
Hazard Ratio for relapse outcome.		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.	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		12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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.		12 months

Collaborators and Investigators

• Sponsor: CareDx

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Relapse; Chimerism
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Anemia; Leukemia; Myelodysplastic Syndromes; Anemia, Refractory; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts
• Other Study ID Numbers: CDNACT2501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This will be discussed and updated at a later time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No