CD34+ Enriched Transplants to Treat Myelodysplastic Syndrome

NCT ID: NCT05617625

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-31

Study Completion Date

2032-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Myelodysplastic Syndromes Graft Vs Host Disease Graft-versus-host-disease

Keywords

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stem cell transplant allogeneic transplant

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

0.8 mg/kg q6h x 12 doses via IV injection on Days -9, -8, and -7 prior to transplant

Melphalan

Intervention Type DRUG

70 mg/m\^2/day x 2 days via IV infusion over 30 minutes on Days -6 and -5 prior to transplant

Fludarabine

Intervention Type DRUG

25 mg/m\^2/days x 5 days via IV infusion over 30 minutes on Days -6, -5, -4, -3, and -2 prior to transplant

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

Intervention Type DEVICE

CliniMACS system will be used to derive CD34+ enriched, T-cell depleted (T-cells limited to 1.0 x 10\^5 CD3+ cells/kg) PBSC for transplant, which will occur on Day 0. PBSC (5 x 10\^6 CD34+ cells/kg) are suspended in a volume of approximately 20-50 mL and delivered via IV infusion over 15 minutes.

Interventions

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Busulfan

0.8 mg/kg q6h x 12 doses via IV injection on Days -9, -8, and -7 prior to transplant

Intervention Type DRUG

Melphalan

70 mg/m\^2/day x 2 days via IV infusion over 30 minutes on Days -6 and -5 prior to transplant

Intervention Type DRUG

Fludarabine

25 mg/m\^2/days x 5 days via IV infusion over 30 minutes on Days -6, -5, -4, -3, and -2 prior to transplant

Intervention Type DRUG

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

CliniMACS system will be used to derive CD34+ enriched, T-cell depleted (T-cells limited to 1.0 x 10\^5 CD3+ cells/kg) PBSC for transplant, which will occur on Day 0. PBSC (5 x 10\^6 CD34+ cells/kg) are suspended in a volume of approximately 20-50 mL and delivered via IV infusion over 15 minutes.

Intervention Type DEVICE

Other Intervention Names

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Busulfex Alkeran Fludara

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Guenther Koehne

OTHER

Sponsor Role lead

Responsible Party

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Guenther Koehne

Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Guenther Koehne, M.D.

Role: PRINCIPAL_INVESTIGATOR

Miami Cancer Institute/Baptist Health South Florida

Locations

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Miami Cancer Institute

Miami, Florida, United States

Site Status

Countries

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United States

References

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Robin M, Porcher R, Ades L, Raffoux E, Michallet M, Francois S, Cahn JY, Delmer A, Wattel E, Vigouroux S, Bay JO, Cornillon J, Huynh A, Nguyen S, Rubio MT, Vincent L, Maillard N, Charbonnier A, de Latour RP, Reman O, Dombret H, Fenaux P, Socie G. HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM. Leukemia. 2015 Jul;29(7):1496-501. doi: 10.1038/leu.2015.37. Epub 2015 Feb 13.

Reference Type BACKGROUND
PMID: 25676424 (View on PubMed)

Saber W, Cutler CS, Nakamura R, Zhang MJ, Atallah E, Rizzo JD, Maziarz RT, Cortes J, Kalaycio ME, Horowitz MM. Impact of donor source on hematopoietic cell transplantation outcomes for patients with myelodysplastic syndromes (MDS). Blood. 2013 Sep 12;122(11):1974-82. doi: 10.1182/blood-2013-04-496778. Epub 2013 Jul 11.

Reference Type BACKGROUND
PMID: 23847196 (View on PubMed)

Smith AR, Baker KS, Defor TE, Verneris MR, Wagner JE, Macmillan ML. Hematopoietic cell transplantation for children with acute lymphoblastic leukemia in second complete remission: similar outcomes in recipients of unrelated marrow and umbilical cord blood versus marrow from HLA matched sibling donors. Biol Blood Marrow Transplant. 2009 Sep;15(9):1086-93. doi: 10.1016/j.bbmt.2009.05.005.

Reference Type BACKGROUND
PMID: 19660721 (View on PubMed)

Moore J, Nivison-Smith I, Goh K, Ma D, Bradstock K, Szer J, Durrant S, Schwarer A, Bardy P, Herrmann R, Dodds A. Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2007 May;13(5):601-7. doi: 10.1016/j.bbmt.2007.01.073. Epub 2007 Mar 23.

Reference Type BACKGROUND
PMID: 17448920 (View on PubMed)

Kernan NA, Collins NH, Juliano L, Cartagena T, Dupont B, O'Reilly RJ. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood. 1986 Sep;68(3):770-3.

Reference Type BACKGROUND
PMID: 3527302 (View on PubMed)

Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, Bader P, Schlegel PG, Greil J, Stachel D, Herzog RJ, Niethammer D. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant. 2001 Apr;27(8):777-83. doi: 10.1038/sj.bmt.1702996.

Reference Type BACKGROUND
PMID: 11477433 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12091376 (View on PubMed)

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.

Reference Type BACKGROUND

Related Links

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Other Identifiers

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2021-KOE-002

Identifier Type: -

Identifier Source: org_study_id