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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001748
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose

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.


Condition Intervention Phase
Graft vs Host Disease Hematologic Neoplasms Lymphoma Myelodysplastic Syndromes Myeloid Leukemia Procedure: Peripheral blood progenitor cell transplant Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: HLA-Mismatched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 35
Study Start Date: June 1998
Estimated Study Completion Date: May 2000
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001748


Locations
United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001748     History of Changes
Other Study ID Numbers: 980122
98-H-0122
First Submitted: November 3, 1999
First Posted: December 10, 2002
Last Update Posted: March 4, 2008
Last Verified: August 1999

Keywords provided by National Institutes of Health Clinical Center (CC):
Cyclophosphamide
Donor Apheresis
Graft vs. Host Disease
Graft-Versus-Leukemia
Leukemic Relapse
Myeloma
Peripheral Blood Stem Cells
Whole Body Irradiation
Acute Lymphoblastic Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
Hematological Malignancies
Myelodysplastic Syndrome
Myeloproliferative Disorders

Additional relevant MeSH terms:
Leukemia
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Hematologic Neoplasms
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Neoplasms by Site