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

February 8, 2008
January 31, 2013
February 2008
February 2014   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00618969 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hematologic Neoplasms
  • Anemia, Aplastic
  • Hemoglobinuria, Paroxysmal
  • Multiple Myeloma
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
Experimental: 1
Non-myeloablative preparative regimen (reduced-intensity) of busulfan, melphalan and alemtuzumab followed by a haploidentical-related peripheral blood stem cell transplant.
Intervention: Other: haploidentical allogeneic PBSC transplant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
February 2014
February 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
No
Contact: Andrew M Yeager, MD 520-626-3191 ayeager@azcc.arizona.edu
Contact: Phyllis Schneider, RN 520-694-9070 pschneider@azcc.arizona.edu
United States
 
NCT00618969
BIO 07-122
Yes
Andrew Yeager, University of Arizona
Andrew Yeager
Not Provided
Principal Investigator: Andrew M Yeager, MD University of Arizona
University of Arizona
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP