Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source
Overview
- Phase
- Phase 1
- Intervention
- Mesna
- Conditions
- Leukemia
- Sponsor
- Rafic Farah, MD
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Acute GvHD
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.
Detailed Description
This is a pilot study to assess the safety and potential efficacy of haploidentical peripheral blood stem cell transplantation using a nonmyeloablative preparative regimen and post-transplant cyclophosphamide. The overall objective of this study is to collect the efficacy and safety data to provide the basis to decide whether a larger study of clinical efficacy is warranted in this setting.
Investigators
Rafic Farah, MD
Assistant Professor of Medicine
University of Pittsburgh
Eligibility Criteria
Inclusion Criteria
- •Molecular based HLA typing will be performed for the HLA-A, -B, -Cw, DRB1 and -DQB1 loci to the resolution adequate to establish haplo identity. A minimum match of 5/10 is required. An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor.
- •Subjects must meet one of the disease classifications listed below:
- •Acute leukemias (includes T lymphoblastic lymphoma). Remission is defined as \< 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with \> 20% cellularity, peripheral blood counts showing ANC \>1000/ul, including patients in CRp.
- •Acute Lymphoblastic Leukemia in high risk CR1 as defined by at least one of the following:
- •Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements White blood cell counts \>30,000/mcL Patients over 30 years of age Time to complete remission \>4 weeks Presence of extramedullary disease
- •Acute Myelogeneous Leukemia in high risk CR1 as defined by at least one of the following:
- •Greater than 1 cycle of induction therapy required to achieve remission Preceding myelodysplastic syndrome (MDS) Presence of Flt3 abnormalities FAB M6 or M7 leukemia or
- •Adverse cytogenetics for overall survival such as:
- •those associated with MDS Complex karyotype (≥ 3 abnormalities) Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 \[alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)\], t(11;19)(q23;p13.1)
- •Acute Leukemias in 2nd or subsequent remission
Exclusion Criteria
- •HLA-matched donor able to donate.
- •Pregnancy or breast-feeding.
- •Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- •Positive anti-donor HLA antibody.
Arms & Interventions
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Mesna
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Total Body Irradiation
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Hematopoietic stem cell infusion
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Fludarabine
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Cyclophosphamide
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Tacrolimus
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: Mycophenolate
Treatment
Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes Day -1 Total Body Irradiation 200 cGy, donor apheresis Day 0 T cell replete PBSC Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses Day 5 Begin tacrolimus ,mycophenolate, and G-CSF
Intervention: G-CSF
Outcomes
Primary Outcomes
Acute GvHD
Time Frame: Day +84
The cumulative incidence of grades III/IV acute GvHD at day +84 will be assessed. The first day of acute GvHD onset will be used to calculate a cumulative incidence curve by certain grade. An overall cumulative incidence curve will be computed along with a 90% CI with graft failure, relapse/progression, and death as competing risks.
Chronic Graft-versus-Host Disease
Time Frame: 1 year
The cumulative incidence of chronic GvHD at one year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with graft failure, relapse/progression, and death as competing risks.
Nonrelapse Mortality (NRM)
Time Frame: 1 year
The cumulative incidence of NRM at 1 year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with relapse/progression as competing risk.
Relapse of Malignancy
Time Frame: 1 year
The cumulative incidence of relapse at 1 year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with NRM as competing risk.
Secondary Outcomes
- Primary graft failure(Day +84)
- Secondary graft failure(Up to 1 year)
- Neutrophil Recovery(Up to day +84)
- Platelet recovery(Up to day +84)
- Donor Cell Engraftment(Day +28, Day >= +84)
- Progression-free Survival(Up to 1 year)
- Infections(Date of onset)