Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant
This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 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).
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Chronic Lymphocytic Leukemia
Peripheral T-Cell Lymphoma
Radiation: Total-body irradiation (TBI)
Drug: Cyclosporine A (CsA)
Drug: Mycophenolate Mofetil (MMF)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Peripheral Blood Stem Cell Transplantation With Minimally Myelosuppressive Regimen of Pentostatin and Low-dose Total-body Irradiation|
- Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting [ Time Frame: days +28 and +70 ] [ Designated as safety issue: No ]the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70.
- Toxicity [ Time Frame: Duration of treatment ] [ Designated as safety issue: Yes ]determination of regimen related toxicity of the combination of Pentostatin and low dose total body irradiation. Treatment related toxicity will be graded using NCI CTC Version 2.0 and GVHD using the standard GVHD grading system.
- Immune Effects [ Time Frame: pretransplant and post transplant days28,70,100 and 12, and 24 months ] [ Designated as safety issue: Yes ]kinetics of hematologic and immunologic reconstitution after allogeneic transplantation
- Incidence of Acute and Chronic Graft-versus-host Disease [ Time Frame: twice weekly until day 100 up to 1 year post transplant ] [ Designated as safety issue: Yes ]Incidence of acute and chronic graft-versus-host disease.Acute GVHD usually occurs during the first three months following transplant. Chronic GVHD usually develops after the third month post-transplant.
- Responses to Therapy [ Time Frame: every 6 mo. up to 2 years ] [ Designated as safety issue: No ]event-free and overall survival at 12 months
|Study Start Date:||December 2000|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: Cohort I
Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day
4 mg/m^2 intravenous(IV)once a day(QD)x3days (days -10, -9, -8)
Other Name: NipentRadiation: Total-body irradiation (TBI)
TBI will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. TBI will be given on day -1.Drug: Cyclosporine A (CsA)
CsA will be given at 2.0 mg/kg intravenous (IV) Q 12hrs on days -1,0,and+1 (total 6 doses) then converted to oral at 2 mg/kg by mouth (PO) twice a day (BID) until day+80, then tapered 10% per week over approximately 3 months if no GVHD for related donor transplants. For unrelated CsA will be given at same dose and schedule until day+100 then tapered by 10% per week if no GVHD
Other Name: NeoralDrug: Mycophenolate Mofetil (MMF)
MMF 15 mg/kg by mouth twice a day (PO BID) will be given from day 0-27 then stopped without tapering for related donor transplants. For unrelated donor transplants MMF will be given at same dose until day+40 then tapered over 2months. in absence of GVHD. Doses will be rounded to nearest 250 mg.Drug: G-CSF
10 mcg/kg/day subcutaneously for at least 4 consecutive days.
Other Name: Leukine
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).
- 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.
- To determine the immunomodulatory effects of pentostatin as part of the conditioning regimen for allogeneic peripheral blood stem cell transplantation.
- To determine the incidence of infections after using a minimally myelosuppressive conditioning regimen.
- To determine the kinetics of hematological and immunological reconstitution after allotransplantation with a minimally myelosuppressive conditioning regimen.
- To determine the incidence of chronic GVHD after using allogeneic peripheral blood stem cell transplantation with a minimally myelosuppressive preparative regimen.
- To evaluate the role of the preparative regimen and donor source (related versus unrelated) on inflammatory cytokine profiles.
- To evaluate blood and where possible, biopsy specimens for a recently identified nuclear protein (molecular weight 44/46) in mononuclear cells obtained from study subjects.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00571662
|United States, Nebraska|
|University of Nebraska Medical Center, Section of Oncology/Hematology|
|Omaha, Nebraska, United States, 68198|
|Principal Investigator:||Gregory Bociek, M.D.||University of Nebraska|