Stem Cell Transplantation for Patients With Graft Failure Following an Allogeneic Transplant, Using Identical or Near Identical Donors and Less Toxic Conditioning With CAMPATH 1H
Stem Cell Transplantation for Patients With Graft Failure Following an Allogeneic Transplant, Using Identical or Near Identical Donors and Less Toxic Conditioning With CAMPATH 1H
To assess the safety, feasibility, and rate of donor engraftment for patients with primary or
 secondary engraftment failure after treatment with fludarabine and CAMPATH 1H used as a
 preparative regimen for HLA-identical sibling blood stem cell transplantation (SCT).

 To assess the safety, feasibility, and rate of donor engraftment for patients with primary or
 secondary engraftment failure after treatment with fludarabine and CAMPATH 1H as a
 preparative regimen for matched unrelated or single antigen mismatched family donor marrow
 transplantation.
Study participants will receive the following treatment:

 Day -5 to -2...Fludarabine 30mg/m2* and CAMPATH** 1H 10mg IV

 Day -1.........Day of rest

 Day 0..........Stem cell transplant (infusion)

 Where possible, patients will receive peripheral blood stem cells. When peripheral stem cells
 are unavailable (e.g. from some unrelated donor centers) or insufficient, bone marrow will be
 substituted. If peripheral blood stem cell collection is performed, the donor will be
 stimulated with G-CSF for 5 days and cells collected and frozen until the stem cell target
 number is obtained prior to the patient beginning the therapy. If a bone marrow harvest is
 performed, this will be performed on Day 0 (infusion day). After transplantation, G-CSF 5
 micrograms/kg/day will be administered SC from day 7 until granulocytes >1000/ul.

 Because CAMPATH-1H infusions will provide a persisting level of antibody over the transplant
 period, it will contribute to anti-GvHD activity. Additional GVHD prophylaxis will consist of
 FK506 administered IV via continuous infusion over 24 hours from Day-2 until engraftment or
 when the patient is able to take by mouth, every 12 hours. This is continued until 6 months
 post-transplantation. The dose is then tapered every 2 weeks until discontinued. All patients
 will receive supportive care (prophylaxis for antimicrobial, antiviral, antifungal and
 Pneumocystis Pneumonia, transfusions of blood products and intravenous gamma globulin and
 routine laboratory testing of chemistry and complete blood counts) as per Cell and Gene
 Therapy Standard Operating Procedures (SOP).

 Donor engraftment will be evaluated via standard bone marrow studies (cytogenetics/DNA
 studies for chimerism) on days 30, 60, 100, 180 and 365 post transplantation. If these
 studies reveal loss of donor cells on two consecutive studies and/or evidence of relapsing
 disease, the donor will undergo a peripheral blood stem cell harvest via G-CSF stimulation.
INCLUSION CRITERIA

 -  Diagnosis of engraftment failure either primary or secondary, following allogeneic
 transplantation. Graft failure is defined as absolute neutrophil count < 500/mm3
 and/or platelet count < 20,000/mm3. Primary graft failure is defined as failure to
 maintain absolute neutrophil count > / = 500/mm3 for 3 consecutive days following
 allogeneic transplantation. Secondary graft failure is defined as failure to sustain
 an absolute neutrophil count > / = 500/mm3 after attainment of primary engraftment or
 failure to sustain platelet count > / = 20,000/mm3 despite neutrophil engraftment. For
 SCID patients, graft failure is defined as failure to recover > / = 500/mm3 T-cells
 and/or failure to generate satisfactory response to in vitro mitogen stimulation. For
 patients with genetic diseases, engraftment failure is defined as donor chimerism
 insufficient to correct or overcome the genetic or metabolic deficiency.

 -  Available Healthy Donor without any contraindications for donation (5/6 or 6/6 related
 donor or 5/6 or 6/6 unrelated donor (molecular typing for DRB1)

 -  Age between birth and 65

 -  For women of childbearing potential, negative pregnancy test

 EXCLUSION CRITERIA

 -  Pregnant and lactating women or women unwilling to use contraception.

 -  Uncontrolled intercurrent infection

 -  Refractory AML or ALL

 -  Untreated Blast Crisis for CML

 -  Uncontrolled High-grade lymphoproliferative disease/lymphoma

 -  Unstable angina and uncompensated congestive heart failure (Zubrod of 3 or greater)

 -  Severe chronic pulmonary disease requiring oxygen (Zubrod of 3 or greater)

 -  Hemodialysis dependent

 -  Active Hepatitis or cirrhosis with total bilirubin, SGOT, or SGPT greater than 3 x
 normal.

 -  Concurrent solid organ malignancy not in remission, except for Stage 0 or A prostate
 cancer.

 -  Unstable Cerebral vascular disease and recent hemorrhagic stroke (less than 6 months)

 -  Active CNS disease from hematological disorder.