Clinical trial NCT04635384: Assessment of Chimerism and Relapse Post Bone Marrow/Hematopoietic Cell Transplant (HCT) Using AlloHeme Test
Official title: Assessment of Chimerism and Relapse Post Bone Marrow/HCT Transplant Using AlloHeme Test (ACROBAT)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Keywords: AML
ALL
MDS
Lead sponsor: CareDx
Sponsor class: INDUSTRY
First posted: 2020-11-19
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants aged \> 18 years old with a diagnosis of AML, ALL, and MDS who will undergo an Allo-HCT will be invited to participate and enrolled into the study at the time initial transplant evaluation or at any time before admission for transplantation.

Brief summary: AlloHeme is a chimerism test service that utilizes NGS technology to analyze SNP loci to quantify donor and recipient cells by measuring genomic DNA. Before transplant, patient and donor peripheral blood sample will be collected to identify informative marker for routine chimerism testing and baseline establishment for AlloHeme. Post-transplant blood or bone marrow samples are obtained and compared to the baseline sample profiles to calculate % chimerism of recipient cells in the blood and/or bone marrow samples. Cell selection from blood and bone marrow samples is applied to evaluate chimerism in specific cell subtypes that are relevant to AML and MDS diseases (CD3+ T lymphocytes, CD33+ Myeloid cells and CD15+ Granulocyte cell subtypes from blood and CD34+ hematopoietic stem cells from bone marrow).

Detailed description: The test will be started from month 1 post HCT and will be performed bi-weekly up to month 3, monthly from month 4-6 and quarterly from month 9 to year 2 for total 15 visits. During each visit, about 18 ml (3.6 teaspoons) of whole blood will be collected into 3 pink BD Hemogard tubes with K2 EDTA additive. In addition to blood collection, the subject will be asked to provide 3ml or 0.6 teaspoon of bone marrow specimens during the routine visits on Day 100(month 3), Day 180 and Day 360 for use in this research study. When bone marrow study is performed, marrow specimen will be collected for AlloHeme test at central lab. Standard chimerism assessment, bone marrow study and MRD test will be performed at each participated institution lab as clinically indicated and based on treating physician's discretion. Method of standard of care chimerism and MRD assessment will be based on each institutional standard protocol. Data related to AlloHeme test, clinical outcomes, PHI and all standard of care of patient management information will be collected from medical records. During the Baseline and pre transplant the following clinical data will be collected: sex, age, donor and recipient demographic, chemotherapy, remission status pre-transplant, donor type, HLA, stem cell source, conditioning regimen type and intensity, cytogenetics test, minimal residual disease, chimerism, T cell depletion and GVHD protocol. Following transplantation, clinical events including death, relapse, second allo-HSCT, DLI as well as the events that impact the chimerism like tapering IST, GVHD and infection will be collected.

Eligibility criteria: Inclusion Criteria:

* Male or female, aged 18 years or above.
* The patient must have one of the following diseases: AML, ALL or MDS
* Eligible for allogeneic hematopoietic stem cell transplant
* Subjects must receive an Allo-HCT from an HLA matched related or unrelated donor or haploidentical donor
* Myeloablative or reduced intensity/non-myeloablative conditioning
* Any GVHD prophylaxis regimen including post-transplantation cyclophosphamide-based or conventional regimen
* The subject must be enrolled prior to Allo-HCT

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

* Has history of prior Allo-HCT
* T cell depleted transplant (Including in vivo and ex vivo T cell depletion)
* Inability to comply with medical recommendations or follow-up
* Donor is identical twin
* Pregnancy

Primary outcomes:
measure: To determine the association between increased mixed chimerism (iMC) detected by AlloHeme and post-transplant relapse in patients with acute leukemia and myelodysplastic syndrome.
timeFrame: Jan-2022
Secondary outcomes:
measure: To determine the association of microchimerism detected by AlloHeme on post-transplant relapse in patients with acute leukemia and myelodysplastic syndrome
timeFrame: Jan-2022
measure: To determine the association between an iMC detected by AlloHeme and disease-free survival (DFS) post-transplant in patients with acute leukemia and myelodysplastic syndrome
timeFrame: Jan-2022
measure: To determine the correlation between peripheral blood chimerism detected by AlloHeme and post-transplant measurable residual disease (MRD) status in patients with acute leukemia and myelodysplastic syndrome
timeFrame: Jan-2022
measure: To compare the performance of post-transplant chimerism measured by AlloHeme versus STR-PCR method for post-transplant relapse prediction in patients with acute leukemia and myelodysplastic syndrome.
timeFrame: Jan-2022
Other outcomes:
Locations:
city: Brisbane
country: United States
facility: University of California Irvine
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Augusta
country: United States
facility: Georgia Cancer Center at Augusta University
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: CareDx
name: Nishant Dwivedi, MD/PhD
role: STUDY_DIRECTOR
References: