Clinical trial NCT05617625: CD34+ Enriched Transplants to Treat Myelodysplastic Syndrome
Official title: A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Graft Vs Host Disease
Graft-versus-host-disease
Keywords: stem cell transplant
allogeneic transplant
Lead sponsor: Baptist Health South Florida
Sponsor class: OTHER
First posted: 2022-11-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate whether processing blood stem cell transplants using an investigational device (the CliniMACS system) results in fewer complications for patients who undergo transplant to treat a blood malignancy (cancer) or blood disorder.

The CliniMACS system will be used to remove immune T-cells from the transplant donor's blood. Immune T-cells contribute to graft versus host disease (GVHD) - a serious complication that can happen after transplant. GVHD occurs when a patient's immune system attacks the donor's cells. The study aims to reduce the number of the donor immune T-cells thereby preventing or reducing the severity of GVHD.


Eligibility criteria: Inclusion Criteria:

* Myelodysplastic syndrome (MDS): Refractory anemia/refractory anemia with ring sideroblasts/refractory cytopenia with multilineage anemia (RA/RARS/RCMA) with high-risk cytogenetic features or transfusion dependence, as well as Refractory Anemia with Excess Blasts Type 1 and 2 (RAEB-1 and RAEB-2)
* Karnofsky (adult) Performance Status of at least 70%
* Adequate organ function measured by:
* Cardiac: asymptomatic or if symptomatic then left ventricular ejection fraction (LVEF) at rest must be 50% and must improve with exercise.
* Hepatic: \< 3x upper limit of normal (ULN) aspartate aminotransferase (AST) and: 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant \[e.g., acute myeloid leukemia (AML) Chloroma obstructing the biliary tree\]. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval e.g., patients with paroxysmal nocturnal hemoglobinuria (PNH), Gilbert's disease or other hemolytic disorders.
* Renal: serum creatinine: \<1.2 mg/dL (normal range 0.7-1.3) or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) \> 5940 mL/min (measured or calculated/estimated).
* Pulmonary: asymptomatic or if symptomatic, diffusion capacity of lung for carbon monoxide (DLCO) 50% of predicted (corrected for hemoglobin).
* Willing to participate and must sign an informed consent form

Exclusion Criteria:

* Pregnant or breast-feeding
* Active viral, bacterial or fungal infection
* Patient seropositive for human immunodeficiency virus (HIV)-I /II; human T-lymphotropic virus (HTLV)-I /II
* Presence of leukemia in the central nervous system (CNS)

Primary outcomes:
measure: Change in incidence of graft vs. host disease (GVHD)
timeFrame: Weekly until 3 months, monthly until 6 months, 12 months, 24 months
measure: Change in severity of acute graft vs. host disease (GVHD)
timeFrame: Weekly until 3 months, monthly until 6 months, 12 months, 24 months
measure: Change in severity of chronic graft vs. host disease (GVHD)
timeFrame: Weekly until 3 months, monthly until 6 months, 12 months, 24 months
measure: Change in incidence of relapse-free mortality (transplant-related mortality)
timeFrame: 6 months, 12 months, 24 months
measure: Change in overall survival
timeFrame: 6 months, 12 months, 24 months
measure: Change in disease-free survival
timeFrame: 6 months, 12 months, 24 months
Secondary outcomes:
measure: Proportion of patients receiving optimal vs. suboptimal CD34+/CD3+ PBSC doses
timeFrame: Day 0
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
Study officials:
affiliation: Miami Cancer Institute/Baptist Health South Florida
name: Guenther Koehne, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la Rubia J, Brunet S, Perez-Oteyza J, Ferra C, Zuazu J, Caballero D, Bargay J, Carvalhais A, Diez JL, Espigado I, Alegre A, Rovira M, Campilho F, Odriozola J, Sanz MA, Sierra J, Garcia-Conde J, Montserrat E; Spanish Group for Allogeneic Peripheral Blood Transplantation (Grupo Espanol de Trasplante Hemopoyetico) and Instituto Portugues de Oncologia-Porto. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood. 2002 Jul 15;100(2):724-7. doi: 10.1182/blood-2001-11-0057.
citation: Devine S, Soiffer R, Pasquini M, et al. HLA-identical sibling matched, CD34+ selected, T cell depleted peripheral blood stem cells following myeloablative conditioning for first or second remission acute myeloid leukemia (AML): Results of blood and marrow transplant clinical trials network (BMT CTN) Protocol 0303. Blood. 2009; 114(22):655.