Myelodysplastic SyndromesNCT05617625
CD34+ Enriched Transplants to Treat Myelodysplastic Syndrome
A study testing Busulfan, Melphalan and Fludarabine in people with Myelodysplastic Syndromes and Graft Vs Host Disease, run by Guenther Koehne at 1 site in United States.
Trial 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 myelodysplastic syndrome (MDS). Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Myelodysplastic Syndromes, Graft Vs Host Disease, Graft-versus-host-disease
- What is being tested?
- Busulfan, Melphalan and Fludarabine
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Jan 2034
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MDS patients who qualify for transplant, for which CD34+ selected, T-cell-depleted allogeneic hematopoietic stem cell transplantation is indicated
- Patients with high-risk features with a score equal to or higher than 4.5 using the IPSS-R.
- Patients with therapy-related MDS and patients with transfusion-dependent MDS are high-risk patient cohorts that are eligible independent of Revised International Prognostic Scoring System (IPSS-R) scoring.
- Patient's age is from ≥18 to ≤72 years old.
- Patients must have an appropriately matched donor (MRD 8/8, MUD 8/8, or MMUD 7/8 [mismatch at HLA-A, B or DR-B1 locus])
- Patients may be of either gender or any ethnic background.
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- Patients must have a Karnofsky (adult) Performance Status of at least 70%
- Patients must have adequate organ function measured by:
- Cardiac: asymptomatic; left ventricular ejection fraction (LVEF) at rest must be ≥ 50%.
- Hepatic: < 3 × upper limit of normal (ULN) aspartate aminotransferase (AST) and < 1.5 × ULN 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. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible for Pl approval e.g., patients with paroxysmal nocturnal hemoglobinuria (PNH), Gilbert's disease, or other hemolytic disorders.
- Renal: serum creatinine: within the normal range 0.7-1.3 mg/dL or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 45 mL/min (measured or calculated/estimated via Cockcroft-Gault formula).
- Pulmonary: asymptomatic [but sustained diffusing capacity of the lungs for carbon monoxide (DLCO) ≥ 50% of predicted (corrected for hemoglobin)].
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
Who cannot join
- Individuals who are pregnant or breastfeeding
- Uncontrolled bacterial, viral, or fungal infections; or known human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C infection.
- Patients cured of Hepatitis C for ≥3 years prior to enrollment are permitted
- Patients with detectable hepatitis B surface antigen (HBsAg) will be excluded. Patients with detectable hepatitis B surface antigen (HBsAg) are excluded. Patients with viral hepatitis B core antibody (HBcAb) positivity, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable and if they are willing to be on hepatitis B antiviral prophylaxis and undergo monitoring for HBV reactivation (every 12 weeks while on immune suppression) per institutional protocols. Patients will be referred promptly to hepatology specialists with the first detectable viral load.
- Symptomatic cardiac disease (angina, congestive heart failure) and/or LVEF <50%
- History of cardiovascular disease, including but not limited to myocardial infarction, unstable angina, stroke, or transient ischemic attack within the 6 months prior to the initiation of study or congestive heart failure (New York Heart Association [NYHA] class III-IV)
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- Patients who subsequently receive a non-T-cell-depleted transplant
- Stem cell count <3.0 × 106/kg following CD34+ selection
- Known sensitivity to components of CliniMACS® Prodigy CD34 System 8. Have a history of other active malignancy(ies) unless the patient has been disease-free for at least 2 years and is deemed by the treating Investigator to be at low risk for recurrence of that malignancy; or the only prior cancer is curatively treated cervical cancer in situ, or basal cell or squamous cell carcinoma of the skin.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Baptist Health Herbert Wertheim Cancer Institute
Miami, Florida, 33176
Guenther Koehne, M.D., (786) 596-2000, GuentherK@baptisthealth.net
About this study
Official title: A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Myelodysplastic Syndrome
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 myelodysplastic syndrome (MDS).
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.
- Being tested
- Busulfan, Melphalan, Fludarabine, CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC)
- Keywords
- stem cell transplant, allogeneic transplant
- Medical subject headings
- Myelodysplastic Syndromes, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex
0.8 mg/kg q6h × 12 doses via IV injection on Days -9, -8, and -7 prior to transplant
MelphalanDrug
Also called Alkeran
70 mg/m²/day × 2 days (50 mg/m²/day is patients ≥65 years with a comorbidity score of ≥3) via IV infusion over 30 minutes on Days -6 and -5 prior to transplant
FludarabineDrug
Also called Fludara
25 mg/m²/days × 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)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.
| Study group | Role | What they receive |
|---|---|---|
| CD34+ Peripheral Blood Progenitor Cell (PBSC) Transplant with Busulfan/Melphalan/Fludarabine Regimen | Experimental | 1. Cytoreduction therapy:
1. 0.8 mg/kg q6h x 12 doses busulfan via IV injection (dose may be modified according to pharmacokinetics)
2. 70 mg/m²/day x 2 days melphalan via IV infusion over 30 minutes
3. 25 mg/m²/day x 5 days fludarabine (50 mg/m²/day in patients ≥65 years with a comorbidity score of ≥3) via IV infusion over 30 minutes
2. CD34+ selected, T-cell depleted, allogeneic PBSC transplant using CliniMACS system to select CD34+ cells Receives: Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine; Device: CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
OS is defined as time from transplant to death due to any cause
Measured: 2 years
Secondary outcomes (5)
Disease-free survival (DFS)
DFS is defined as the time from transplant to relapse, progression, death due to any cause, whichever occurs first.
Measured: 2 years
Transplant-related mortality (TRM)
Incidence of TRM defined as mortality related to the transplant rather than the disease
Measured: 2 years
Acute graft vs. host disease (GVHD)
Incidence of acute GvHD as graded using the International Bone Marrow Transplant Registry Severity Index, which includes assessment of skin, liver, and gut, grading each's severity from 0 to 4 (higher numbers reflecting the more severe disease). The overall assessment is based on the involvement and severity of each of the areas. A = Stage 1 skin involvement, no liver or gut involvement; B = Stage 2 skin involvement, Stage 1 to 2 gut or liver involvement; C = Stage 3 skin, liver or gut involvement; D = Stage 4 skin, liver, or gut involvement.
Measured: 2 years
Chronic graft vs. host disease (GVHD)
Incidence of chronic GvHD as graded using the NIH scoring system, which includes assessment of skin, mouth, eyes, GI tract, liver, lungs, joint/fascia, and genital tract and grades the severity of affected organs from 0 to 3 (higher scores reflecting the more severe disease). The overall assessment is based on the number of organs/sites with clinically significant functional impairment (i.e., score 2-3). No GVHD = no organs/sites with significant functional impairment; Mild GVHD = involves two or fewer organs/sites with significant functional impairment; Moderate GVHD = involves three or more organs/sites with significant functional impairment -OR- involves one or zero organs/sites with NO significant functional impairment; Severe GVHD = Major disability caused by chronic GVHD.
Measured: 2 years
Proportion of patients receiving optimal vs. suboptimal CD34+/CD3+ PBSC doses
Proportion of patients receiving optimal CD34+ (>5 × 10^6/kg) and CD3+ (< 5 ×10^4/kg) cell doses versus the proportion recurring suboptimal doses (<3 × 10^6/kg) CD34+ cells; and the proportion of patients receiving CD3+ T-cell doses (>5 × 10^4/kg)
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2022
- Study startJan 2027 (estimated)
- Primary completionJan 2034 (estimated)
- Study completionJan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guenther Koehne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Guenther Koehne, Baptist Health South Florida
- Investigators
- Guenther Koehne, M.D., Ph.D., Principal investigator, Baptist Health Herbert Wertheim Cancer Insitute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05617625
- Sponsor's protocol ID
- 2021-KOE-002
- Status last verified
- Sep 2026
- First submitted
- 8 Nov 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25676424Saber 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.
PubMed 23847196Smith 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.
PubMed 19660721Moore 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.
PubMed 17448920Kernan 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.
PubMed 3527302Handgretinger 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.
PubMed 11477433Urbano-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.
PubMed 12091376Devine 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.