Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

• Status: Terminated
• Trial end date: 2010-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Blood disorders such as leukemia or lymphoma or hemoglobinopathies can benefit from receiving an allogeneic (meaning that the cells are from a donor) stem cell transplant. Stem cells are created in the bone marrow. They grow into different types of blood cells that the body needs, including red blood cells, white blood cells, and platelets. In a transplant, the body's stem cells would be killed and then replaced by stem cells from the donor. Usually, patients are given very high doses of chemotherapy (drugs which kill cancer cells) prior to receiving a stem cell transplant. However, patients that are older, have received several prior treatments, or have other organ diseases are at a high risk of getting life-threatening treatment-related side effects from high doses of chemotherapy. Over the past several years, some doctors have begun to use lower doses of chemotherapy for preparing patients for a stem cell transplant.

A condition that can occur after a stem cell transplant from a donor is Graft Versus Host Disease (GVHD). It is a rare but serious disorder that can strike persons whose immune system is suppressed and have received either a blood transfusion or a bone marrow transplant. Symptoms may include skin rash, intestinal problems similar to inflammation of the bowel and liver dysfunction.

This research study uses a combination of lower-dose chemotherapy agents that is slightly different from those that have been used before.

The medicines that will be used in this study are Fludarabine, Busulfan, both chemotherapy medicines, and Campath. Campath is a monoclonal antibody (a type of substance produced in the laboratory that binds to cancer cells). It helps the immune system see the cancer cell as something that needs to be destroyed.

This research study will help us learn if using Fludarabine, Busulfan and Campath prior to an allogeneic stem cell transplant can provide treatment for blood disorders while decreasing the incidence of side effects.

• 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; The Methodist Hospital Research Institute; The Methodist Hospital System
• Treatments: Alemtuzumab; Busulfan; Fludarabine; Fludarabine phosphate; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

1. Diagnosis of myelodysplastic and myeloproliferative disorders, acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, multiple myeloma, plasma cell dyscrasia, lymphoproliferative disorders (non-Hodgkin lymphoma, hairy cell leukemia, chronic lymphocytic leukemia, and Hodgkin's disease) and non malignant hematologic diseases considered treatable with an allogeneic transplant including but not limited to bone marrow failure syndrome, hemoglobinopathy and severe immunodeficiency states.

2. Performance status 0-2 on Zubrod scale

3. Ejection fraction > 30%

4. AST/ALT and bilirubin not > 4 times normal

5. FEV1 greater than 1.0 and diffusion capacity > 40%

6. Age birth to 70 years of age

7. Conditions that increase treatment related mortality (need more than one to be eligible):

• Age > 35 years

• EF of less than 45%

• DLCO less than 50% or FEV1 50-75% of predicted value

• Diabetes mellitus

• Renal insufficiency, defined by increase in serum creatinine level of 1.5 times ULN or decrease in GFR by 25%

• Prior recent history of systemic fungal infection

• 3rd or greater remission of AML or ALL

• More than 1 year of diagnosis (CML or myeloma patients only)

• Multiple types of treatment regimens (equal to or more than 3)

• Prior autologous or allogeneic stem cell transplantation

• Significant Grade III or IV neurologic or hepatic toxicity as defined by NCI CTC toxicity from previous treatment

• No matched sibling donor

8. Available healthy donor without any contraindications for donation

• 5/6 or 6/6 related

• 5/6 or 6/6 unrelated (molecular typing for DRB1)

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

10. For women of childbearing potential, negative pregnancy test

Exclusion Criteria:

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

2. HIV positive patient.

3. Uncontrolled intercurrent infection.

4. Refractory AML or ALL.

5. Untreated blast crisis for CML.

6. Uncontrolled high-grade lymphoproliferative disease/lymphoma.

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

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

9. Hemodialysis dependent.

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

11. Serum creatinine >2x ULN.

12. Unstable cerebral vascular disease and recent hemorrhagic stroke (less than 6 months).

13. Active CNS disease from hematological disorder.