CD34+ Enriched Transplants to Treat Myelodysplastic Syndrome

Guenther Koehne

Status and phase: Suspended; Phase 2

Conditions: Graft Vs Host Disease; Myelodysplastic Syndromes; Graft-versus-host-disease

Treatments: Device: CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC); Drug: Melphalan; Drug: Busulfan; Drug: Fludarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT05617625

2021-KOE-002

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

CD34+ Peripheral Blood Progenitor Cell (PBSC) Transplant with Busulfan/Melphalan/Fludarabine Regimen

Experimental group

Description:

1. Cytoreduction therapy: 1. 0.8 mg/kg q6h x 12 doses busulfan via IV injection 2. 70 mg/m\^2/day x 2 days melphalan via IV infusion over 30 minutes 3. 25 mg/m\^2/day x 5 days fludarabine vis IV infusion over 30 minutes 2. CD34+ selected, T-cell depleted, allogeneic PBSC transplant using CliniMACS system to select CD34+ cells

Treatment:

Drug: Fludarabine

Drug: Busulfan

Drug: Melphalan

Device: CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC)