Know Cancer

or
forgot password

Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies - Role of Cyclosporine


Phase 2
10 Years
55 Years
Not Enrolling
Both
Chronic Lymphocytic Leukemia, Graft vs Host Disease, Hematologic Neoplasm, Multiple Myeloma, Myelodysplastic Syndrome

Thank you

Trial Information

Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T-Cell Add-Back for Hematological Malignancies - Role of Cyclosporine


Bone marrow stem cell transplant studies carried out by the NHLBI BMT Unit have focused on
approaches to optimize the stem cell and lymphocyte dose in order to improve transplant
survival and increase the graft-vs.-leukemia effect. A CD34 stem cell dose of greater than
3 x 10(6)/kg was found to increase survival and reduce relapse, while a CD3+ lymphocyte dose
of less than 1 x 10(5)/kg was associated with a very low incidence of GVHD. Although
processing of 2 peripheral blood progenitor cell (PBPC) collections with the CellPro
immunoabsorption method (combined CD34-positive selection and CD2-negative selection)
provided an improvement over previous methods, the system did not always achieve these
optimal cell doses. A recent preclinical evaluation by the Department of Transfusion
Medicine of a new immunomagnetic cell selection system available from Nexell, Inc. has
demonstrated improved recovery of CD34+ cells and increased depletion of T lymphocytes,
compared to the CellPro method. Incorporation of the Nexell system (Isolex 300i) into this
clinical protocol will allow us to more consistently achieve CD34+ cell doses above the
threshold of 3 x 10(6)/kg and CD3+ lymphocyte dosing in the region of 0.5 x 10(5)/kg. This
will make it possible to test (1) the potential benefit of optimized transplant cell doses,
(2) elimination of post transplant immunosuppression to enhance immune recovery.

In this study, we will use the Nexell Isolex 300i system to obtain more data on the
relationship between CD34+ stem cell dose and outcome. In recipients who receive a T cell
dose less than 0.5 x 10(5) CD3+ cells/kg the effect of withdrawing cyclosporine on
development of GVHD will be evaluated in a cohort study: 20 patients will receive low dose
cyclosporine. If the incidence of grade II or worse GVHD is 10% or less, no post transplant
immunosuppression will be given to the next cohort and the incidence and severity of acute
GVHD again assessed. Stopping rules for unacceptable GVHD severity will be applied. Two
match groups HLA 6/6 and 5/6 donor-recipient pairs will be separately studied using this
approach.

In a second phase of the study we will continue to accumulate data on T lymphocyte add-back
given on day 45 and day 100 after transplant. For this phase, cyclosporine will be
reintroduced on day 44 and continued until day 120 to accelerate immune recovery.

Up to 70 patients aged between 10 and 55 years will be studied in each subset (HLA 6/6 and
5/6 matched cohorts). The major endpoint of the study is acute GVHD after transplant. We
will also measure engraftment, acute and chronic GVHD, leukemic relapse, transplant-related
and all causes of mortality, cytomegalovirus reactivation and leukemia-free survival.
Patients will be followed for a minimum of 5 years.

Inclusion Criteria


- INCLUSION CRITERIA - Patient:

Ages 10-55 years.

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

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

Acute myelogenous leukemia (AML): AML in first remission except AML with good risk
karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8;21). All AML in second or
subsequent remission, primary induction failure and resistant relapse.

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

Myeloproliferative disorders (myelofibrosis, polycythemia vera, essential thrombocythemia)
in transformation to acute leukemia.

Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky
progressive disease or with thrombocytopenia (less than or equal to 100,000 / mcl) or
anemia (less than or equal to 10g/dl) not due to recent chemotherapy.

No major organ dysfunction precluding transplantation.

DLCO greater than or equal to 60% predicted.

Left ventricular ejection fraction: greater than or equal to 40% predicted.

ECOG performance status of 0 or 1.

For adults: Written informed consent given by adults. For minors: Written informed
consent from one parent or guardian. Informed oral consent from minors: The process will
be explained to the minor on a level of complexity appropriate for their age and ability
to comprehend.

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

EXCLUSION CRITERIA - Recipient (any of the following):

Patient pregnant.

Age less than 10 and greater than 55 years.

ECOG performance status of 2 or more.

Severe psychiatric illness in the patient or donor. Mental deficiency sufficiently severe
as to make compliance with the treatment unlikely, and making informed consent impossible.

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

DLCO less than 60% predicted.

Left ventricular ejection fraction: less than 40% predicted.

Serum creatinine greater than 3mg/dl.

Serum bilirubin greater than 4 mg/dl.

Transaminases greater than 3x upper limit of normal.

HIV positive (donor or recipient).

History of other malignancies except basal cell or squamous carcinoma of the skin,
positive PAP smear and subsequent negative follow up.

Individuals with diseases listed above as eligible for this protocol, but where debility
or age makes the risk of intensive myeloablative therapy unacceptable. These patients
will be considered for a non-myeloablative allogeneic transplantation protocol (97-H-0202,
99-H-0050).

INCLUSION CRITERIA - Donor:

HLA 6/6 identical or 5/6 (one antigen mismatched) family donor.

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

For adults: Written informed consent given by adults. For minors: Written informed
consent from one parent or guardian. Informed oral consent from minors: The process will
be explained to the minor on a level of complexity appropriate for their age and ability
to comprehend.

EXCLUSION CRITERIA - Donor (any of the following):

Pregnant or lactating.

Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance
with the BMT treatment unlikely, and making informed consent impossible.

HIV positive.

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 (and before D45 add-back).

Outcome Time Frame:

Day 45

Safety Issue:

Yes

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:

990046

NCT ID:

NCT00001873

Start Date:

February 1999

Completion Date:

December 2007

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Graft Vs Host Disease
  • Hematologic Neoplasm
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Peripheral Blood Stem Cells
  • Cyclosporine
  • Cyclosphosphamide
  • Whole Body Irradiation
  • Donor Apheresis
  • Leukemic Relapse
  • Graft vs. Host Disease
  • Graft-Versus-Leukemia
  • Graft-Versus-Myeloma
  • Chronic Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndromes
  • Multiple Myeloma
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin's Lymphoma
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892