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

March 1, 2016 updated by: University of Arizona

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Arizona Cancer Center/University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: haploidentical allogeneic PBSC transp

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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).
by day +100 (i.e., 100 days after haploidentical PBSCT).

Secondary Outcome Measures

Outcome Measure
Time Frame
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
non-relapse mortality at day +100

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arizona

Investigators

  • Principal Investigator: Andrew M Yeager, MD, University of Arizona

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

February 1, 2016

Study Registration Dates

First Submitted

February 8, 2008

First Submitted That Met QC Criteria

February 8, 2008

First Posted (Estimate)

February 20, 2008

Study Record Updates

Last Update Posted (Estimate)

March 3, 2016

Last Update Submitted That Met QC Criteria

March 1, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BIO 07-122

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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