Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation of Patients With Hematological Diseases

• Status: Completed
• Trial end date: 2006-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Participants in this study have a hematologic malignancy (a disorder in the bone marrow that affects the body's ability to create blood) that might benefit from receiving an allogeneic stem cell transplant (meaning the cells come from a donor) from a family member or nearly identical matched donor. The donor may either be a matched sibling, a mismatched family member, or an unrelated person.

Usually these patients are given high doses of chemotherapy before receiving a stem cell transplant to keep their immune system from rejecting the donor stem cells and to kill any diseased cells that remain in the body. However, this group of patients have a high risk of developing possibly life-threatening treatment-related side effects such as infections, damage to vital organs such as lungs, liver, kidney and heart, as well as graft versus host disease (GVHD).

Instead of the high dose chemotherapy and radiotherapy usually given before a transplant, this research study uses a new pre-transplant combination of three drugs, Fludarabine, Anti-CD45 and CAMPATH-1H with low dose radiotherapy. Fludarabine is a chemotherapy drug while Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells, including those which are causing this disease. CAMPATH-1H is particularly important because it stays active in the body for a long time after it is given, which means it may work longer to prevent GVHD symptoms. Anti-CD45 may help in eradicating residual malignant cells. All these agents also help in preventing rejection of donor stem cells. This study is designed to give a less intense chemotherapy and radiotherapy, so that the life-threatening toxicities of conventional high dose chemotherapy and radiotherapy regimen can be reduced, while maintaining the ability to cure cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; Texas Children's Hospital; The Methodist Hospital Research Institute; The Methodist Hospital System
• Treatments: Alemtuzumab; Fludarabine; Tacrolimus

Criteria

Inclusion Criteria:

1. Patients with one of the following high risk diseases needing allogeneic hemopoietic stem cell transplantation:

Acute myeloid leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse

Acute lymphoblastic leukemia either a) Primary refractory, or b) Beyond first complete remission(CR1), or c) In CR1 with high risk of relapse

Chronic myeloid leukemia, either a) Accelerated phase, or b) Blast crisis, or c) Chronic phase and not achieving major cytogenetic response despite standard therapy

Chronic lymphocytic leukemia, either a) Primary refractory, or b) Beyond first complete remission(CR1),

Non Hodgkin's lymphoma, either a) Primary refractory, or b) Beyond first complete remission(CR1)

Hodgkin's disease, either a) Primary refractory, or b) Beyond first complete remission(CR1),

Myelodysplastic syndrome with IPSS score > 0. (Appendix A)

Myeloproliferative disorders (with the exclusion of chronic myeloid leukemia) a) Primary Myelofibrosis with Lile score of 1 or 2 (Appendix B) b) Polycythemia Vera or Essential Thrombocythemia transformed to AML or Myelofibrosis and PV "spent phase"

Multiple Myeloma with stage II or III disease

Severe aplastic anemia

2. Conditions that increase Treatment Related Mortality (need one or more to be eligible):

Greater or equal to 35 years of age;

Ejection Fraction of less than 50%;

DLCO less than 50% or FEV1/FVC < 80% of predicted value;

Diabetes Mellitus;

Renal insufficiency (serum creatinine abnormal);

Hepatic dysfunction-transaminases, or alkaline phosphatase, or bilirubin twice the upper limit of normal;

Prior recent history of systemic fungal infection;

Multiple prior treatment regimens (equal to or more than 3);

Significant Grade III or IV neurologic, cardiac, pulmonary, renal or hepatic toxicity from previous treatment;

Prior Autologous or Allogeneic Stem Cell transplantation;

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

4. Patient and/or responsible person able to understand and sign consent

Exclusion Criteria:

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

HIV positive patient

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

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

Child's class C cirrhosis

Unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)

Patients with known allergy to rat serum products