Back to resultsDonor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases
Primary Purpose
Graft Versus Host Disease, Hematopoietic/Lymphoid Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
busulfan
cyclophosphamide
allogeneic hematopoietic stem cell transplantation
tacrolimus
mycophenolate mofetil
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care
- Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies.
- Ages 18-69 years old.
- Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor
Exclusion Criteria:
- Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)
- Positive pregnancy test for women of childbearing age.
- Major anticipated illness or organ failure incompatible with survival form transplant.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
Sites / Locations
- Comprehensive Cancer Center of Wake Forest University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (stem cell transplant with GVHD prophylaxis)
Arm Description
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2 TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation
Outcomes
Primary Outcome Measures
12 Month Disease Free Survival Probability
The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
Secondary Outcome Measures
Rate of Acute GvHD
Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval.
Overall Survival
The survival function will be estimated and plotted using the method of Kaplan and Meier.
Progression Free Survival
Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year.
Relapse-free Mortality
Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk.
Full Information
NCT ID
NCT02248597
First Posted
September 23, 2014
Last Updated
October 10, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02248597
Brief Title
Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases
Official Title
Haploidentical Stem Cell Transplant Using Post Transplant Cyclophosphamide for GvHD Prophylaxis: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
February 25, 2015 (Actual)
Primary Completion Date
January 18, 2022 (Actual)
Study Completion Date
January 18, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This pilot clinical trial studies donor stem cell transplant followed by cyclophosphamide in treating patients with hematological diseases. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine if haploidentical stem cell transplant using post-transplant cyclophosphamide results in 60% or better disease free survival (DFS) at 12 months at our institution.
SECONDARY OBJECTIVES:
I. To determine the rate of acute and chronic graft-versus-host disease (GvHD), non-relapse mortality, and relapse.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate intravenously (IV) once daily (QD) on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35.
After completion of study treatment, patients are followed up periodically for 2 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Hematopoietic/Lymphoid Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (stem cell transplant with GVHD prophylaxis)
Arm Type
Experimental
Arm Description
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV QD on days -6 to -2. Patients receiving myeloablative conditioning receive busulfan IV every 6 hours for 16 doses on days -7 to -4 and patients receiving reduced intensity conditioning receive busulfan IV every 6 hours for 8 doses on days -5 to -4. Patients also receive cyclophosphamide IV QD on days -3 and -2
TRANSPLANT: Patients undergo stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclophosphamide QD on days 3 and 4, tacrolimus on days 5-180, and mycophenolate mofetil on days 5-35. Allogeneic hematopoietic stem cell transplantation
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
BSF, BU, Misulfan, Mitosan, Myeloleukon
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo myeloablative or reduced intensity allogeneic stem cell transplant
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Other Intervention Name(s)
FK 506, Prograf
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Primary Outcome Measure Information:
Title
12 Month Disease Free Survival Probability
Description
The percentage of patients who experience death or disease relapse by one year will be calculated and a corresponding 95% confidence interval will be constructed using the normal approximation for binomial proportions. The survival function will be estimated and plotted using the method of Kaplan and Meier.
Time Frame
At 12 months
Secondary Outcome Measure Information:
Title
Rate of Acute GvHD
Description
Kaplan-Meier estimation of the rate of acute GvHD in the study population at one year with a 95% confidence interval.
Time Frame
12 months
Title
Overall Survival
Description
The survival function will be estimated and plotted using the method of Kaplan and Meier.
Time Frame
At 12 months
Title
Progression Free Survival
Description
Kaplan-Meier estimation of the percentage of patients who are alive without progressive disease at one year.
Time Frame
At 12 months
Title
Relapse-free Mortality
Description
Non-relapse mortality will be defined as time from registration to death due to anything other than relapse of hematological malignancy. Patients who relapse will be treated as a competing risk.
Time Frame
At 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of a hematological malignancy requiring an allogeneic stem cell transplant consistent with the standard of care
Remission of any acute hematologic malignancy or adequate disease control for chronic malignancies.
Ages 18-69 years old.
Available familial haploidentical (4 to 6 out of 8 HLA loci-matched) donor
Exclusion Criteria:
Significant organ dysfunction defined as: LV EF < 50% (evaluated by echocardiogram or MRI), DLCO or FEV1 < 65% predicted, AST/ALT > 2.5 x ULN, Bilirubin > 1.5 x ULN, Serum creatinine > 2mg/dL, dialysis, or prior renal transplant
HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation)
Positive pregnancy test for women of childbearing age.
Major anticipated illness or organ failure incompatible with survival form transplant.
Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dianna S. Howard
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Comprehensive Cancer Center of Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Donor Stem Cell Transplant Followed by Cyclophosphamide in Treating Patients With Hematological Diseases
We'll reach out to this number within 24 hrs