Allogeneic Peripheral Blood Stem Cell Transplantation With Minimally Myelosuppressive Regimen of Pentostatin and Low-dose Total-body Irradiation
This is a pilot study which began with a plan to enroll 50 patients (20 related and 30
unrelated donor transplants) with hematological malignancy assessing the safety and efficacy
of a minimally myelosuppressive regimen with Pentostatin and low-dose total body irradiation
(TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT).
Patients with persistent or progressive malignancy after transplantation will be treated
with GM-CSF (cytokine therapy) to assess its toxicity and potential therapeutic efficacy.
Patients with persistent or progressive disease who fail or do not qualify for the cytokine
therapy portion of the study will become candidates for donor leukocyte infusions.
The purpose of this protocol remains a pilot study which is now regarded as a phase II trial
with a plan to enroll 40 ADDITIONAL patients (20 related and 20 unrelated donor
transplants) with hematological malignancy assessing the safety and efficacy of a modified
version of the original preparative regimen of Pentostatin and low-dose total body
irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation
(alloPSCT). Patients who fail will become candidates for donor-leukocyte infusion (DLI).
1. To determine the safety of treating hematological malignancies by establishing donor
hematopoietic chimerism using pentostatin and low-dose total body irradiation followed
by allogeneic peripheral blood stem cell transplantation.
2. To determine the immunomodulatory effects of pentostatin as part of the conditioning
regimen for allogeneic peripheral blood stem cell transplantation.
1. To determine the incidence of infections after using a minimally myelosuppressive
2. To determine the kinetics of hematological and immunological reconstitution after
allotransplantation with a minimally myelosuppressive conditioning regimen.
3. To determine the incidence of chronic GVHD after using allogeneic peripheral blood stem
cell transplantation with a minimally myelosuppressive preparative regimen.
4. To evaluate the role of the preparative regimen and donor source (related versus
unrelated) on inflammatory cytokine profiles.
5. To evaluate blood and where possible, biopsy specimens for a recently identified
nuclear protein (molecular weight 44/46) in mononuclear cells obtained from study
Interventions, evaluation, and follow up will include:
Pentostatin 4 mg/m^2/d intravenously once a day x 3 days will be administered with 1000 cc
NS hydration before and after pentostatin ten days prior to stem cell infusion (days -10,
-9, and -8). Total-body irradiation (TBI): TBI 2.0 Gy will be given on day -1. Antiemetics
will be given as needed. Patients will receive one liter normal saline over 2 hours pre TBI.
A bone marrow biopsy and aspiration with cytogenetics and flow cytometry will be performed
on Day +28, Day +70 and 6, 12, 18 and 24 months following the transplant to monitor
hematologic recovery. DNA fingerprinting will also be conducted at the same time at 3, 4,
5, 6, 12, 18, and 24 months to determine chimerism.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting
the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70.
days +28 and +70
Gregory Bociek, M.D.
University of Nebraska
United States: Institutional Review Board
|University of Nebraska Medical Center, Section of Oncology/Hematology||Omaha, Nebraska 68198-7680|