Back to resultsCD34+ Enriched Transplants to Treat Myelodysplastic Syndrome
Primary Purpose
Myelodysplastic Syndromes, Graft Vs Host Disease, Graft-versus-host-disease
Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Busulfan
Melphalan
Fludarabine
CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC)
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring stem cell transplant, allogeneic transplant
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)
Sites / Locations
- Miami Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CD34+ Peripheral Blood Progenitor Cell (PBSC) Transplant with Busulfan/Melphalan/Fludarabine Regimen
Arm Description
Cytoreduction therapy: 0.8 mg/kg q6h x 12 doses busulfan via IV injection 70 mg/m^2/day x 2 days melphalan via IV infusion over 30 minutes 25 mg/m^2/day x 5 days fludarabine vis IV infusion over 30 minutes CD34+ selected, T-cell depleted, allogeneic PBSC transplant using CliniMACS system to select CD34+ cells
Outcomes
Primary Outcome Measures
Change in incidence of graft vs. host disease (GVHD)
Incidence of acute and chronic GVHD
Change in severity of acute graft vs. host disease (GVHD)
Severity 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.
Change in severity of chronic graft vs. host disease (GVHD)
Severity 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.
Change in incidence of relapse-free mortality (transplant-related mortality)
Incidence of relapse-free mortality, defined as mortality related to the transplant rather than the disease
Change in overall survival
Incidence of overall survival, defined as time from transplant to death or last follow-up.
Change in disease-free survival
Incidence of disease-free survival, defined as the minimum time interval of relapse/recurrence, to death or to the last follow-up, from the time of transplant.
Secondary Outcome Measures
Proportion of patients receiving optimal vs. suboptimal CD34+/CD3+ PBSC doses
Proportion of patients receiving optimal CD34+ (>5 x 10^6/kg) and CD3+ (< 5 x10^4/kg) cell doses versus the proportion recurring suboptimal doses (<3 x 10^6/kg) CD34+ cells; and the proportion of patients receiving CD3+ T-cell doses (>5 x 10^4/kg)
Full Information
NCT ID
NCT05617625
First Posted
November 8, 2022
Last Updated
October 5, 2023
Sponsor
Baptist Health South Florida
1. Study Identification
Unique Protocol Identification Number
NCT05617625
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Suspended
Why Stopped
The study has been put on hold while pending CMS approval
Study Start Date
March 2024 (Anticipated)
Primary Completion Date
March 2031 (Anticipated)
Study Completion Date
March 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baptist Health South Florida
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Graft Vs Host Disease, Graft-versus-host-disease
Keywords
stem cell transplant, allogeneic transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CD34+ Peripheral Blood Progenitor Cell (PBSC) Transplant with Busulfan/Melphalan/Fludarabine Regimen
Arm Type
Experimental
Arm Description
Cytoreduction therapy:
0.8 mg/kg q6h x 12 doses busulfan via IV injection
70 mg/m^2/day x 2 days melphalan via IV infusion over 30 minutes
25 mg/m^2/day x 5 days fludarabine vis IV infusion over 30 minutes
CD34+ selected, T-cell depleted, allogeneic PBSC transplant using CliniMACS system to select CD34+ cells
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
0.8 mg/kg q6h x 12 doses via IV injection on Days -9, -8, and -7 prior to transplant
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
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
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
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
Device
Intervention Name(s)
CliniMACS CD34+ enriched, T-cell depleted peripheral blood stem cell (PBSC)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in incidence of graft vs. host disease (GVHD)
Description
Incidence of acute and chronic GVHD
Time Frame
Weekly until 3 months, monthly until 6 months, 12 months, 24 months
Title
Change in severity of acute graft vs. host disease (GVHD)
Description
Severity 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.
Time Frame
Weekly until 3 months, monthly until 6 months, 12 months, 24 months
Title
Change in severity of chronic graft vs. host disease (GVHD)
Description
Severity 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.
Time Frame
Weekly until 3 months, monthly until 6 months, 12 months, 24 months
Title
Change in incidence of relapse-free mortality (transplant-related mortality)
Description
Incidence of relapse-free mortality, defined as mortality related to the transplant rather than the disease
Time Frame
6 months, 12 months, 24 months
Title
Change in overall survival
Description
Incidence of overall survival, defined as time from transplant to death or last follow-up.
Time Frame
6 months, 12 months, 24 months
Title
Change in disease-free survival
Description
Incidence of disease-free survival, defined as the minimum time interval of relapse/recurrence, to death or to the last follow-up, from the time of transplant.
Time Frame
6 months, 12 months, 24 months
Secondary Outcome Measure Information:
Title
Proportion of patients receiving optimal vs. suboptimal CD34+/CD3+ PBSC doses
Description
Proportion of patients receiving optimal CD34+ (>5 x 10^6/kg) and CD3+ (< 5 x10^4/kg) cell doses versus the proportion recurring suboptimal doses (<3 x 10^6/kg) CD34+ cells; and the proportion of patients receiving CD3+ T-cell doses (>5 x 10^4/kg)
Time Frame
Day 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guenther Koehne, M.D.
Organizational Affiliation
Miami Cancer Institute/Baptist Health South Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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25676424
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Citation
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CD34+ Enriched Transplants to Treat Myelodysplastic Syndrome
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