Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Arizona
Sponsor:
Information provided by (Responsible Party):
Andrew Yeager, University of Arizona
ClinicalTrials.gov Identifier:
NCT00618969
First received: February 8, 2008
Last updated: January 31, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to transplant haploidentical related peripheral blood stem cells (PBSCs) that come from a relative such as a parent, sibling, a child or other relative who has a half-matched tissue type with the recipient (rather than being completely matched) following administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab.


Condition Intervention Phase
Hematologic Neoplasms
Anemia, Aplastic
Hemoglobinuria, Paroxysmal
Multiple Myeloma
Other: haploidentical allogeneic PBSC transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors for Treatment of Hematologic Malignancies and Hematopoietic Failure States

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • 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. [ Time Frame: by day +100 (i.e., 100 days after haploidentical PBSCT). ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the safety of haploidentical related allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. [ Time Frame: non-relapse mortality at day +100 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: February 2008
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Non-myeloablative preparative regimen (reduced-intensity) of busulfan, melphalan and alemtuzumab followed by a haploidentical-related peripheral blood stem cell transplant.
Other: haploidentical allogeneic PBSC 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

Other Names:
  • Myleran,
  • Busulfex,
  • Busulphan
  • Alkeran,
  • L-PAM, L-Sarcolysin,
  • Phenylalanine Mustard
  • MABCAMPATH®,
  • CAMPATH®
  • partially matched family related donor transplant

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618969

Contacts
Contact: Andrew M Yeager, MD 520-626-3191 ayeager@azcc.arizona.edu
Contact: Phyllis Schneider, RN 520-694-9070 pschneider@azcc.arizona.edu

Locations
United States, Arizona
Arizona Cancer Center/University Medical Center Recruiting
Tucson, Arizona, United States, 85719
Contact: Andrew M Yeager, MD    520-626-3191    ayeager@azcc.arizona.edu   
Contact: Phyllis Schneider, RN    520-694-9070    pschneider@azcc.arizona.edu   
Principal Investigator: Andrew M Yeager, MD         
Sponsors and Collaborators
Andrew Yeager
Investigators
Principal Investigator: Andrew M Yeager, MD University of Arizona
  More Information

No publications provided

Responsible Party: Andrew Yeager, Professor of Medicine and Pediatrics, University of Arizona
ClinicalTrials.gov Identifier: NCT00618969     History of Changes
Obsolete Identifiers: NCT00840424
Other Study ID Numbers: BIO 07-122
Study First Received: February 8, 2008
Last Updated: January 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arizona:
Haploidentical
peripheral blood stem cell transplantation
leukemia
myeloma
Hodgkin's disease
non-Hodgkin's lymphoma

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Neoplasms
Hemoglobinuria
Hemoglobinuria, Paroxysmal
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Hematologic Diseases
Bone Marrow Diseases
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Busulfan
Melphalan

ClinicalTrials.gov processed this record on July 26, 2014