HLA-Mismatched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematological Malignancies

March 3, 2008 updated by: National Heart, Lung, and Blood Institute (NHLBI)

Many patients with hematological malignancies potentially curable by bone marrow transplantation are not considered for transplantation because an HLA identical family or unrelated donor is unavailable. For these patients the only curative option is a transplant from a partially matched family donor. Such transplants are feasible but are less successful than matched sibling donor transplants. The main problems with mismatched transplants are graft rejection, graft-vs-host disease, and regimen-related mortality. This restricts the use of mismatched transplants to patients less than 45 years at high risk of dying from the hematological malignancy.

This protocol evaluates a new preparative regimen designed to ensure stem cell engraftment by increased immunosuppression, followed by a G-CSF mobilized T cell depleted, stem cell rich, peripheral blood progenitor cell (PBPC) transplant from a mismatched related donor in patients with high risk hematological malignancies.

This phase I study evaluates engraftment and GVHD following T cell depleted, HLA-mismatched PBPC transplants. Stopping rules will be used to make modifications to the protocol in the event of graft failure.

The end points of the study are graft take, acute and chronic GVHD, leukemic relapse, transplant-related mortality, death and leukemia-free survival. Patients will be followed up for 5 years. It is planned to treat up to 35 patients aged between 10 and 45 years.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Many patients with hematological malignancies potentially curable by bone marrow transplantation are not considered for transplantation because an HLA identical family or unrelated donor is unavailable. For these patients the only curative option is a transplant from a partially matched family donor. Such transplants are feasible but are less successful than matched sibling donor transplants. The main problems with mismatched transplants are graft rejection, graft-vs-host disease, and regimen-related mortality. This restricts the use of mismatched transplants to patients less than 45 years at high risk of dying from the hematological malignancy.

This protocol evaluates a new preparative regimen designed to ensure stem cell engraftment by increased immunosuppression, followed by a G-CSF mobilized T cell depleted, stem cell rich, peripheral blood progenitor cell (PBPC) transplant from a mismatched related donor in patients with high risk hematological malignancies.

This phase I study evaluates engraftment and GVHD following T cell depleted, HLA-mismatched PBPC transplants. Stopping rules will be used to make modifications to the protocol in the event of graft failure.

The end points of the study are graft take, acute and chronic GVHD, leukemic relapse, transplant-related mortality, death and leukemia-free survival. Patients will be followed up for 5 years. It is planned to treat up to 35 patients aged between 10 and 45 years.

Study Type

Interventional

Enrollment

35

Phase

  • Phase 1

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
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Heart, Lung and Blood Institute (NHLBI)

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Patient:

Ages 10-45 years.

Chronic myelogenous leukemia, any of these categories: accelerated phase or blast transformation.

Acute lymphoblastic leukemia, any of these categories: Adults (greater than 18 years) in any remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia). All second remissions, primary induction failure including partial remission, partially responding or untreated relapse.

Acute myelogenous leukemia (AML): All AML in second or subsequent remission, primary induction failure or partial remission and resistant relapse.

Myelodysplastic syndromes, any of these categories: refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia.

Myeloproliferative disorders undergoing transformation to terminal stages.

Chronic lymphocytic leukemia (CLL) in Richter transformation.

High-grade lymphoma, refractory to standard treatment approaches, mantle cell lymphoma.

No major organ dysfunction precluding transplantation.

DLCO greater than 65% predicted.

Left ventricular ejection fraction: greater than 40% predicted.

ECOG performance status of 0 or 1.

Informed consent given. Informed consent from parents for minors.

Women of childbearing age with a negative pregnancy test may participate.

Donor:

Partially HLA matched family donor (3-5/6 matches).

Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, and no history of stroke).

Informed consent given.

Patients or donors must not be pregnant or nursing.

Must not have ECOG performance status of 2 or more.

No severe psychiatric illness in patient or donor: Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.

No major anticipated illness or organ failure incompatible with survival from BMT.

DLCO must not be less than 65% predicted.

No left ventricular ejection fraction: less than 40% predicted.

Must not have serum creatinine greater than 3 mg/dl.

Must not have serum bilirubin greater than 4 mg/dl, Transaminases greater than 3 times the upper limit of normal.

Donor or patient must not be HIV positive.

Must not have history of other malignancies except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up.

Donor must be fit to receive G-CSF and undergo apheresis.

Must not fail to mobilize adequate numbers of CD34+ cells after two cycles of G-CSF.

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

Collaborators and Investigators

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

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 1998

Study Completion

May 1, 2000

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

December 9, 2002

First Posted (Estimate)

December 10, 2002

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

August 1, 1999

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 980122
  • 98-H-0122

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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