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Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults


Phase 2
55 Years
71 Years
Not Enrolling
Both
Chronic Lymphocytic Leukemia, Graft vs Host Disease, Leukemia, Myelodysplastic Syndrome, Myeloid Leukemia

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Trial Information

Low Intensity Preparative Regimen Followed by HLA-Matched, Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in Older Adults


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.

Inclusion 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).

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Principal Investigator

A. John Barrett, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Heart, Lung, and Blood Institute (NHLBI)

Authority:

United States: Federal Government

Study ID:

970202

NCT ID:

NCT00001637

Start Date:

September 1997

Completion Date:

July 2008

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Graft Vs Host Disease
  • Leukemia
  • Myelodysplastic Syndrome
  • Myeloid Leukemia
  • 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
  • Graft vs Host Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892