Back to resultsCD34+ Transplants for Leukemia and Lymphoma
Primary Purpose
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Total Body Irradiation (TBI)
Thiotepa
Cyclophosphamide
Busulfan
Melphalan
Fludarabine
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Stem Cell Transplant
Eligibility Criteria
Inclusion Criteria:
Malignant conditions or other life-threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
- AML in 1st remission - for patients who is AML does not have 'good risk' cytogenetic features (i.e. t8:21, t 15: 17, inv16).
- Secondary AML in 1st remission
- AML in 1st relapse or 2nd remission
- ALL/CLL in patient remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission
- CML failing to respond to or not tolerating imatinib or dasatinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.
Non-Hodgkin's lymphoma with chemo responsive disease in any of the following categories:
- Intermediate or high-grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
- Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
- Chronic myelomonocyte leukemia: CMML-1 and CMML-2.
The following inclusion criteria are also required:
- Patient's age includes from ≥18 to ≤74 years old.
- Patients may be of either gender or any ethnic background.
- Patients must have a Karnofsky (adult) Performance Status of at least 70%
- Patients must have adequate organ function measured by:
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be 50% and must improve with exercise.
Hepatic: < 3x ULN AST and: s 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. 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 PNH, Gilbert's disease or other hemolytic disorders.
Renal: serum creatinine: s; 1.2 mg/dL or if serum creatinine is outside the normal range, then CrCl > 30 ml/min (measured or calculated/estimated).
Pulmonary: asymptomatic or if symptomatic, 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.
Exclusion Criteria:
- Female patients who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Patient seropositive for HIV-I /II; HTLV -I /II
- Presence of leukemia in the CNS
Sites / Locations
- Baptist Health South Florida/Miami Cancer Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Regimen A: TBI/Thiotepa/Cyclophosphamide
Regimen B: Busulfan/Melphalan/Fludarabine
Arm Description
Patients in enrolled in Regimen A will receive the following: Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m^2 x 5 days may be substituted)
Patients in enrolled in Regimen B will receive the following: Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease Melphalan, 70 mg/m^2/day x 2 days via IV infusion over 30 minutes daily Fludarabine, 25 mg/m^2/day x 5 days via IV infusion over 30 minutes daily
Outcomes
Primary Outcome Measures
Incidence rate of graft versus host disease (GvHD)
Incidence of acute and chronic GvHD
Severity of disease
Severity of the adverse events will be reported based on the CTCAE Version 5.
Incidence of transplant-related mortality (TRM)
TRM includes fatal complications resulting from the allogeneic transplant and/ or treatment regimens such as graft failure, GvHD, hemorrhages, and infections.
Change in overall survival (OS)
OS is defined as time from transplant to death or last follow-up.
Change in disease free survival (DFS)
DFS is defined as the minimum time interval of times to relapse/recurrence, to death or to the last follow- up, from the time of transplant.
Secondary Outcome Measures
Proportion of patients optimal and suboptimal doses
The proportion of patients receiving optimal cell doses (CD34+: >5x 10^6/kg and CD3+: < 5 x10^4/kg) and suboptimal doses (CD34+: <3 x 10^6/kg and CD3+: >5 x 10^4/kg).
Full Information
NCT ID
NCT05565105
First Posted
September 28, 2022
Last Updated
September 26, 2023
Sponsor
Baptist Health South Florida
1. Study Identification
Unique Protocol Identification Number
NCT05565105
Brief Title
CD34+ Transplants for Leukemia and Lymphoma
Official Title
A Phase II Trial of CD34+ Enriched Transplants From HLA-Compatible Related or Unrelated Donors for Treatment of Patients With Leukemia or Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
December 2030 (Anticipated)
Study Completion Date
December 2030 (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
No
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 less complications for patients undergoing transplant for treatment of a blood malignancy (cancer) or blood disorder.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute
Keywords
Stem Cell Transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Regimen A: TBI/Thiotepa/Cyclophosphamide
Arm Type
Experimental
Arm Description
Patients in enrolled in Regimen A will receive the following:
Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding
Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day
Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m^2 x 5 days may be substituted)
Arm Title
Regimen B: Busulfan/Melphalan/Fludarabine
Arm Type
Experimental
Arm Description
Patients in enrolled in Regimen B will receive the following:
Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease
Melphalan, 70 mg/m^2/day x 2 days via IV infusion over 30 minutes daily
Fludarabine, 25 mg/m^2/day x 5 days via IV infusion over 30 minutes daily
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation (TBI)
Intervention Description
Hyper-fractioned TBI is administered by a linear accelerator at a dose rate of < 15 cGy/minute.
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
Thioplex
Intervention Description
Thiotepa: 5 mg/kg/day IV over approximately 4 hours daily x 2 (Day -5 and Day -4).
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Cyclophosphamide: 60 mg/kg/day x 2 or Fludarabine 25 mg/m^2 x 5 if cyclophosphamide is contraindicated
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
Busulfan: 0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
Melphalan: 70 mg/m^2/day x 2
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine: 25 mg/m^2/day x 5
Primary Outcome Measure Information:
Title
Incidence rate of graft versus host disease (GvHD)
Description
Incidence of acute and chronic GvHD
Time Frame
Two years
Title
Severity of disease
Description
Severity of the adverse events will be reported based on the CTCAE Version 5.
Time Frame
Two years
Title
Incidence of transplant-related mortality (TRM)
Description
TRM includes fatal complications resulting from the allogeneic transplant and/ or treatment regimens such as graft failure, GvHD, hemorrhages, and infections.
Time Frame
Two years
Title
Change in overall survival (OS)
Description
OS is defined as time from transplant to death or last follow-up.
Time Frame
Six months, one year, two years
Title
Change in disease free survival (DFS)
Description
DFS is defined as the minimum time interval of times to relapse/recurrence, to death or to the last follow- up, from the time of transplant.
Time Frame
Six months, one year, two years
Secondary Outcome Measure Information:
Title
Proportion of patients optimal and suboptimal doses
Description
The proportion of patients receiving optimal cell doses (CD34+: >5x 10^6/kg and CD3+: < 5 x10^4/kg) and suboptimal doses (CD34+: <3 x 10^6/kg and CD3+: >5 x 10^4/kg).
Time Frame
Two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Malignant conditions or other life-threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
AML in 1st remission - for patients who is AML does not have 'good risk' cytogenetic features (i.e. t8:21, t 15: 17, inv16).
Secondary AML in 1st remission
AML in 1st relapse or 2nd remission
ALL/CLL in patient remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL 2nd remission
CML failing to respond to or not tolerating imatinib or dasatinib in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.
Non-Hodgkin's lymphoma with chemo responsive disease in any of the following categories:
Intermediate or high-grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
Any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
Chronic myelomonocyte leukemia: CMML-1 and CMML-2.
The following inclusion criteria are also required:
Patient's age includes from ≥18 to ≤74 years old.
Patients may be of either gender or any ethnic background.
Patients must have a Karnofsky (adult) Performance Status of at least 70%
Patients must have adequate organ function measured by:
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be 50% and must improve with exercise.
Hepatic: < 3x ULN AST and: s 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. 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 PNH, Gilbert's disease or other hemolytic disorders.
Renal: serum creatinine: s; 1.2 mg/dL or if serum creatinine is outside the normal range, then CrCl > 30 ml/min (measured or calculated/estimated).
Pulmonary: asymptomatic or if symptomatic, 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.
Exclusion Criteria:
Female patients who are pregnant or breast-feeding
Active viral, bacterial or fungal infection
Patient seropositive for HIV-I /II; HTLV -I /II
Presence of leukemia in the CNS
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guenther Koehne, MD, PhD
Phone
786-596-2000
Email
GuentherK@baptisthealth.net
First Name & Middle Initial & Last Name or Official Title & Degree
Antonio Marrero-Ochoa, RN
Phone
786-596-2000
Email
antonio.marreoochoa@baptisthealth.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guenther Koehne, MD, PhD
Organizational Affiliation
Baptist Health South Florida/Miami Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baptist Health South Florida/Miami Cancer Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guenther Koehne, MD, Ph.D.
Phone
786-596-2000
Email
GuentherK@baptisthealth.net
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
15753458
Citation
Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7.
Results Reference
background
PubMed Identifier
11477433
Citation
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.
Results Reference
background
PubMed Identifier
12091376
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.
Results Reference
background
PubMed Identifier
17717135
Citation
Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC, Perales MA, Collins N, Cisek C, Chiu M, van den Brink MR, O'Reilly RJ, Papadopoulos EB. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood. 2007 Dec 15;110(13):4552-9. doi: 10.1182/blood-2007-06-093880. Epub 2007 Aug 23.
Results Reference
background
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CD34+ Transplants for Leukemia and Lymphoma
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