- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00618969
Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors
A Phase II Study of Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors for Treatment of Hematologic Malignancies and Hematopoietic Failure States
Studieöversikt
Status
Intervention / Behandling
Detaljerad beskrivning
Fewer than 35% of patients who might benefit from allogeneic HCT have an HLA-identical sib. Transplantation of peripheral blood stem cells (PBSCs) or bone marrow (BM)from HLA-matched or one-locus mismatch unrelated volunteer donors may be an alternative in some patients who lack HLA-matched sib donors. Despite increasing numbers of volunteer unrelated donors in national and international registries, identification of suitable unrelated donors who are matched with the recipient at all HLA-A, -B, -C and -DRB1 loci (8/8 HLA match) or mismatched at one of those loci (7/8 HLA match) is still challenging, especially for patients who are African-American or multiracial. Additionally, the 3- to 4-month delay between initiation of unrelated donor search to HCT is unacceptably long in patients with aggressive hematologic malignancies that are likely to relapse or progress during that interval. Transplantation of single or dual unrelated umbilical cord blood cells (UCB) units is another alternative, although problems with inadequate cell doses, delayed engraftment, graft rejection and infection persist in adult recipients of unrelated UCB transplants.
This is a phase II single-arm open-label study to evaluate the efficacy and safety of haploidentical related allogeneic PBSCT using a nonmyeloablative preparative regimen of intravenous busulfan (Busulfex®), intravenous melphalan (Alkeran®) and intravenous alemtuzumab (Campath®) in subjects who are candidates for related or unrelated allogeneic hematopoietic cell transplantation (HCT; transplantation of bone marrow or PBSCs) but who lack histocompatible related or unrelated donors. This study will also evaluate immunological reconstitution following haploidentical PBSCT by measurement of circulating T cell receptor excision circle (TREC)-positive cells, an indicator of thymic output. Systematic analyses of TREC-positive cells have not been performed in recipients of haploidentical PBSCT after the preparative regimen described in this protocol.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
-
-
Arizona
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Tucson, Arizona, Förenta staterna, 85719
- Arizona Cancer Center/University Medical Center
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Age between 18 years and 75 years.
- one of these diagnoses: acute myeloid leukemia in remission or relapse, acute lymphocytic leukemia in remission or relapse, chronic myeloid leukemia, chronic lymphocytic leukemia, Hodgkin's disease or non-Hodgkin's lymphoma, multiple myeloma, myelodysplastic syndrome, severe aplastic anemia, or paroxysmal nocturnal hemoglobinuria.
- Subjects with hematologic malignancies must have received at least one previous course of chemotherapy or biological therapy (i.e., a subject cannot be enrolled on this study for initial treatment of the malignancy).
- Absence of a healthy related or unrelated volunteer allogeneic donor with whom the subject is either completely HLA matched at HLA-A, -B, -C and -DRB1 (8/8 HLA match) or mismatched at no more than one HLA locus (7/8 HLA match).
- Availability of a healthy haploidentical relative (parent, sib or child) who is able to donate peripheral blood stem cells by apheresis.
Exclusion Criteria:
- Eligibility for another clinical therapeutic protocol or standard-of-care treatment that offers higher probability of cure or long-term control of subject's malignancy.
- Availability of a related or unrelated 7/8 or 8/8 HLA-matched allogeneic donor.
- Severe organ dysfunction
- Untreated or progressive central nervous system involvement by malignancy.
- Subject is pregnant or breast feeding.
- Karnofsky score below 50.
- Seropositivity for human immunodeficiency virus (HIV).
- Life expectancy less than 12 weeks with conventional treatments.
- For subjects who are fertile, refusal to practice contraception upon entering this study and for at least 12 months after PBSCT or after cessation of post-transplant immunosuppressive treatments, whichever occurs later.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Haploidentical allogeneic PBSC transp
Non-myeloablative preparative regimen (reduced-intensity) of busulfan, melphalan and alemtuzumab followed by a haploidentical-related peripheral blood stem cell transplant.
|
Days -5 and -4: IV busulfan 3.2 mg/kg/dose daily for 2 days Day -3: IV melphalan 100 mg/m2 as a single dose Days -2 and -1: IV alemtuzumab 30 mg/dose daily for 2 days Day 0: Transplantation of haploidentical related allogeneic peripheral blood stem cells (PBSCs)- target cell dose 10 x 106 donor CD34+ cells per kilogram of recipient weight
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood)in peripheral blood by day +100.
Tidsram: by day +100 (i.e., 100 days after haploidentical PBSCT).
|
by day +100 (i.e., 100 days after haploidentical PBSCT).
|
Sekundära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
To determine the safety of haploidentical related allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab.
Tidsram: non-relapse mortality at day +100
|
non-relapse mortality at day +100
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Andrew M Yeager, MD, University of Arizona
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Neoplasmer efter plats
- Urologiska sjukdomar
- Urologiska manifestationer
- Benmärgssjukdomar
- Hematologiska sjukdomar
- Hemorragiska störningar
- Urineringsstörningar
- Hemostatiska störningar
- Paraproteinemier
- Blodproteinstörningar
- Anemi
- Neoplasmer, Plasmacell
- Proteinuri
- Anemi, hemolytisk
- Benmärgsfel
- Myelodysplastiska syndrom
- Hematologiska neoplasmer
- Multipelt myelom
- Anemi, aplastisk
- Hemoglobinuri
- Hemoglobinuri, Paroxysmal
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Antineoplastiska medel
- Immunsuppressiva medel
- Immunologiska faktorer
- Antineoplastiska medel, Alkylering
- Alkyleringsmedel
- Myeloablativa agonister
- Melphalan
- Busulfan
Andra studie-ID-nummer
- BIO 07-122
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