search
Back to results

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

Primary Purpose

Graft vs Host Disease, Hematologic Neoplasms, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Peripheral blood progenitor cell transplant
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft vs Host Disease focused on measuring 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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Heart, Lung and Blood Institute (NHLBI)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
March 3, 2008
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00001748
Brief Title
HLA-Mismatched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematological Malignancies
Official Title
HLA-Mismatched Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
August 1999
Overall Recruitment Status
Completed
Study Start Date
June 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft vs Host Disease, Hematologic Neoplasms, Lymphoma, Myelodysplastic Syndromes, Myeloid Leukemia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
35 (false)

8. Arms, Groups, and Interventions

Intervention Type
Procedure
Intervention Name(s)
Peripheral blood progenitor cell transplant

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
National Heart, Lung and Blood Institute (NHLBI)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
7528570
Citation
Lane TA, Law P, Maruyama M, Young D, Burgess J, Mullen M, Mealiffe M, Terstappen LW, Hardwick A, Moubayed M, et al. Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation. Blood. 1995 Jan 1;85(1):275-82.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs