Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001637
First received: November 3, 1999
Last updated: April 8, 2014
Last verified: March 2014
  Purpose

Diseases such as leukemia, lymphoma, and multiple myeloma fall into the category of blood cancers. Some of these conditions can now be cured by bone marrow transplantation (BMT). The ability of BMT to cure these conditions has been credited to the use of high doses of chemotherapy, radiation therapy, and the antileukemia effect of the transplant.

Because the effectiveness of BMT relies on the use of high doses of chemotherapy and total body irradiation (TBI), it is a therapy associated with toxic side effects. These side effects are often deadly and have limited BMT for use in patients under the age of 55.

In this study researchers plan to treat older patients between the ages of 55 to 75 years with blood cell transplants taken from donors who are genetically matched relatives of the patient. In order to decrease the toxic side effects associated with the transplant, researchers will not use chemoradiotherapy. Instead they plan to use intensive immunosuppressive therapy and allow the transplanted cells to take effect.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Graft vs Host Disease
Leukemia
Myelodysplastic Syndrome
Myeloid Leukemia
Procedure: Blood cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults

Resource links provided by NLM:


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

Primary Outcome Measures:
  • The proportion of patients with clinically significant acute GHVD (Grade II or higher) following the T depleted PBPC transplant.

Enrollment: 28
Study Start Date: September 1997
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Blood cell transplantation
    N/A
Detailed Description:

Patients with adult leukemias, non-Hodgkin's lymphoma and multiple myeloma, can now be cured by allogeneic bone marrow transplantation (BMT). This curative effect has been ascribed to the use of high dose chemoradiotherapy and the antileukemia effect of the graft.

The assumption that BMT relies on the myeloablative effect of high dose chemotherapy and total body irradiation (TBI), has largely restricted allogeneic bone marrow transplantation in adults to those under the age of 55 years. Toxicity related mortality increases progressively with age and although some transplant centers carry out BMT in patients up to the age of 60 years, it is generally accepted that treatment related mortality prohibits the use of allogeneic bone marrow transplantation in patients beyond the age of 55 years.

Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8 positive lymphocytes with specific reactivity for the patients leukemia and a potent graft versus leukemia (GVL) effect. This GVL effect is best seen in patients with relapse CML after bone marrow transplantation where a single infusion of donor lymphocytes can induce complete remission.

In this protocol, we treat older patients between the ages of 55 to 71 years with hematologic disorders with an allogeneic stem cell transplant from an HLA identical sibling, using intensive immunosuppressive regimen without myeloablation in attempts to decrease the transplant related toxicity while preserving the antileukemia effect of the graft. The low intensity nonmyeloablative conditioning regimen will provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid immune reconstitution. We will add back lymphocytes in patients with less than 75% donor marrow chimerism as an attempt to prevent graft rejection.

The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GVHD, transplant related morbidity and mortality as well as survival.

  Eligibility

Ages Eligible for Study:   55 Years to 71 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA - PATIENT:

Ages 55-71 years.

Chronic myelogenous leukemia (CML): chronic phase.

Acute lymphoblastic leukemia (ALL), all patients in complete or partial remission.

Acute myelogenous leukemia (AML): AML in first complete or partial remission. Exceptions: AML with good risk karyotypes: AML M3 t(5;17), AML M4Eo (inv. 16), AML t(8;21). All AML in second or subsequent complete remission.

Myelodyplastic syndromes: refractory anemia with excess of blasts (less than 10%) or early transformation to acute leukemia or Chronic myelomonocytic leukemia.

Chronic lymphocytic leukemia (CLL) with bulky or progressive disease despite prior treatment with chemotherapy which includes purine analogs.

Mantle cell lymphoma.

Relapsed or progressive non-Hodgkins lymphoma, failing standard treatment approaches and unsuitable for autologous stem cell transplantation.

No major organ dysfunction precluding transplantation.

DLCO greater than or equal to 40% predicted.

Left ventricular ejection fraction: greater than 30% predicted.

ECOG performance status of 0-2.

INCLUSION CRITERIA - DONOR:

HLA identical family donor, up to 75 years old.

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

Informed consent given.

EXCLUSION CRITERIA:

Patient or donor pregnant or lactating.

Patient age less than 55, greater than 71 years.

ECOG performance status of 3 or more. Psychiatric disorder or mental deficiency of the patient or the donor sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from BMT.

DLCO less than 40% predicted.

Left ventricular ejection fraction less than 30% predicted.

Serum creatinine greater than 2.5 mg/dl.

Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal.

HIV positive (donor or recipient). Donors who are positive for HBV, HCV, or HTLV will be used at the discretion of the investigator.

Other malignant diseases liable to relapse or progress within 5 years.

Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of heart failure or unstable angina, platelet count less than 90,000/cu mm).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001637

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: A. John Barrett, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001637     History of Changes
Other Study ID Numbers: 970202, 97-H-0202
Study First Received: November 3, 1999
Last Updated: April 8, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Peripheral Blood Stem Cells
Engraftment
Fludarabine
Nonmyeloablative
Graft-Versus-Leukemia
Graft vs. Host Disease
Cyclophosphamide
Donor Apheresis
Nonmyeloablative Bone Marrow Transplantation
Chronic Myelogenous Leukemia (CML)
Acute Lymphoblastic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Myelodysplastic Syndromes
Chronic Lymphocytic Leukemia (CLL)
Prolymphocytic Leukemia

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions

ClinicalTrials.gov processed this record on October 30, 2014