ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT0000114400000100-H-0001NCT00001144Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous LeukemiaNon-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Chronic Phase CMLNational Heart, Lung, and Blood Institute (NHLBI)NIH
This study will investigate the safety and effectiveness of a new stem cell transplant
procedure for treating chronic myelogenous leukemia (CML).
Transplantation of donated stem cells (cells produced by the bone marrow that mature into the
different blood components-white cells, red cells and platelets) is a very effective
treatment for CML. However, despite its success in a large number of patients, there is still
a significant risk of death from the procedure. In addition, it results in sterility and
leaves patients at increased risk for other cancers and for eye cataracts. These
complications result from the intensive chemotherapy and radiation patients receive before
the transplant to rid the body of cancer cells. In this study, radiation will not be used and
chemotherapy drugs will be given in lower doses to try to reduce the dangers of the
procedure.
Patients with CML will be tested for matching with a donor (family member) and will undergo a
medical history, physical examination and several tests (e.g., breathing tests, X-rays, and
others) to determine eligibility for the study. Participants will then undergo apheresis to
collect lymphocytes (white blood cells important in the immune system). In apheresis, whole
blood is drawn through a needle in the arm, similar to donating a unit of blood. The required
component-in this case, lymphocytes-are separated and removed, and the rest of the blood is
returned through a needle in the other arm.
Each day starting five days before the transplant, the donor will be given an injection of
G-CSF, a drug that releases stem cells from the bone marrow into the blood stream. The cells
will be collected after the fifth injection and again after a sixth injection the following
day. Meanwhile, patients will be given cyclophosphamide and fludarabine, and perhaps
anti-thymocyte globulin, to prevent rejection of the donated cells.
On the day of the transplant, patients will be given cyclosporin to prevent
graft-versus-host-disease, a disease in which the donor cells react against the patient's
cells. They may also be given lymphocytes after the transplant to boost the immune system and
destroy leukemia cells. After 30, 60 and 100 days, bone marrow cells and circulating
lymphocytes will be checked to see how many are of donor cell origin. If less than 100
percent are of donor origin, more lymphocytes will be transfused. Patients will have physical
examinations and blood tests at least weekly for 3 months and then periodically for 5 years.
CML is a disease which progresses to blast crisis within five years of onset despite medical
intervention. Allogeneic transplantation has provided a definitive cure for a large number of
patients. The International Bone Marrow transplant registry reports a 67% three-year disease
free survival for CML patients receiving a matched sibling transplant. However there remains
a 17-20% treatment-related mortality and significant long-term complications. Myeloablative
regimens with total body irradiation (TBI) are associated with certain sterility, along with
a significant incidence of cataracts and second malignancies. Efforts to ameliorate this
toxicity have led to the development of regimens lacking total body irradiation. Although the
follow-up period for patients receiving these regimens has not been long enough to answer the
question of long-term toxicity, it appears that the response rate and the disease free
survival are comparable to regimens containing TBI. In addition, transplantation experience
with aplastic anemia where TBI is not part of the regimen indicates that treatment related
mortality along with the risk of long-term sequela are significantly decreased.
Non-myeloablative allogeneic peripheral blood stem cell transplants are currently being
investigated in phase I/II trials assessing engraftment efficacy and toxicity at a number of
transplant centers. Preliminary data, including our own experience with 30 patients
undergoing this type of procedure, has shown a high rate of complete donor engraftment with a
low toxicity profile. Two recent studies investigating non-myeloablative allo-transplantation
in standard risk patients revealed an extremely low rate of transplant-related complications
and mortality.
In this protocol we investigate non-myeloablative allogeneic PBSC transplantation in patients
with CML. The patient group under study would include all patients with chronic phase CML
having an HLA-identical sibling. In this protocol, eligible patients would be treated with an
allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA
antigen-mismatched family donor, using an intensive immunosuppressive regimen without
myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities
while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low
intensity non-myeloablative conditioning regimen should 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 reconstitution. We will add back lymphocytes in patients
with less than 100% donor T-cell chimerism in an attempt to prevent graft rejection and
enhance a graft-versus-malignancy effect.
The primary endpoint of this study is transplant related mortality (1 year survival). Other
end points include engraftment, degree of donor-host chimerism, incidence of acute and
chronic graft versus host disease (GVHD), transplant related morbidity, as well as
disease-free and overall survival.
CompletedOctober 1999October 2002Phase 2InterventionalNoTreatment50Chronic Myeloid LeukemiaGraft vs Host DiseaseDrugModified bone marrow stem cell transplantation
PATIENTS:
Patients in chronic phase CML.
Age 10 to 50.
Informed consent given.
Availability of HLA identical or single HLA-locus mismatched family donor.
Females must not be pregnant or lactating.
Must not have ECOG performance status of 3 or more. Must not have a psychiatric disorder or
mental deficiency severe as to make compliance with the BMT treatment unlikely, and making
informed consent impossible.
Must not have major anticipated illness or organ failure incompatible with survival from
PBSC transplant.
Must not have diffusion capacity of carbon monoxide (DLCO) less than 40% predicted.
Must not have left ventricular ejection fraction: less than 30%.
Must not have serum creatinine greater than 50% above normal as defined by age.
Must not have serum bilirubin greater than 4 mg/dl.
Must not have transaminases greater 5 x upper limit of normal.
Must not have other malignant diseases liable to relapse or progress within 5 years.
DONOR:
HLA identical or single HLA-locus mismatched family donor, up to 80 years old.
Informed consent given.
Females must not be pregnant or lactating.
Donor must be fit to receive G-CSF and undergo apheresis. (No controlled hypertension, no
history of congestive heart failure or unstable angina, thrombocytopenia).
Must be HIV negative. Donors who are positive for hepatitis B (HBV), hepatitis C (HBC) or
human T-cell lymphotropic virus (HTLV)-I will be used at the discretion of the
investigator.
AllN/AN/ANoNational Heart, Lung and Blood Institute (NHLBI)BethesdaMaryland20892United StatesUnited StatesRingden O, Remberger M, Ruutu T, Nikoskelainen J, Volin L, Vindelov L, Parkkali T, Lenhoff S, Sallerfors B, Mellander L, Ljungman P, Jacobsen N. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. Blood. 1999 Apr 1;93(7):2196-201.10090927Stucki A, Leisenring W, Sandmaier BM, Sanders J, Anasetti C, Storb R. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Blood. 1998 Oct 15;92(8):2742-9.9763558Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.8114836October 2002November 3, 1999November 3, 1999November 4, 1999October 6, 2008October 6, 2008October 7, 2008Peripheral Blood Stem CellsEngraftmentGraft vs. Host DiseaseGraft-Versus-LeukemiaGraft-Versus-Tumor/MelanomaChronic Myelogenous LeukemiaLeukemiaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveGraft vs Host Disease