Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this research study is to determine whether an experimental drug called AMD3100 used in combination with another medication called G-CSF is safe and can help to increase the amount of blood stem cells (called CD34+ stem cells) found in the peripheral blood of patients with Fanconi anemia. While AMD3100 has been used successfully in adult volunteers and cancer patients, it has not been used in children or patients with Fanconi anemia and in only a few children with cancer.

Fanconi anemia is a rare genetic disease. Most Fanconi anemia patients eventually develop bone marrow failure, a condition in which the bone marrow no longer produces red blood cells (to carry oxygen), white blood cells (to fight infection), and platelets (to help blood clot). The only successful treatment for patients with Fanconi anemia with bone marrow failure is bone marrow transplantation. However, this treatment has many risks and is not available to all patients with Fanconi anemia.

CD34+ cells include stem cells found in the bone marrow or peripheral blood which are capable of making the red blood cells, white blood cells, and platelets. CD34+ stem cells can be collected from bone marrow or peripheral blood and purified using an experimental device called the CliniMACS. However, most Fanconi anemia patients do not have enough CD34+ stem cells in their bone marrow or peripheral blood to be collected using standard methods that work well in children and adults who don't have Fanconi anemia.

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

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: JM 3100; Plerixafor

Criteria

Inclusion Criteria:

1. Patients must have had a diagnosis of Fanconi anemia confirmed by a positive test for increased chromosomal breakage with mitomycin C or diepoxybutane from peripheral blood, bone marrow or amniotic fluid.

2. Bone marrow biopsy/aspirate with cellularity (mononuclear cells per ml of bone marrow obtained), CD34+ content (% of MNC), and normal cytogenetics within three months of collection.

3. For the first two cohorts: Absolute neutrophil count > 750/mm3, Hemoglobin > 8 gm/dl without transfusion, platelet count > 50,000/mm3 without transfusion (within 30 days prior to bone marrow collection or PB stem cell mobilization). For the final cohort, the platelet count will be >30,000/mm3 without transfusion (within 30 days prior to bone marrow collection or PB stem cell mobilization).

4. Minimum weight: 7.5 kg.

5. Age:

First cohort - > 7 Second cohort - > 3 Third cohort - >1.

6. Ability of patient or parent/legal guardian to consent for bone marrow harvest.

7. Ability of patient or parent/legal guardian to consent for placement of temporary apheresis catheter.

8. Ability of patient or parent/legal guardian to consent for apheresis collection.

9. Ability of patient or parent/legal guardian to consent for PRBC/platelet transfusions.

Exclusion Criteria:

1. Myeloid or lymphoid leukemia.

2. Clonal cytogenetic abnormality of bone marrow or peripheral blood lymphocytes (in >2 metaphases by G-banded karyotype or any chromosome deletions of chromosome 7 by Fluorescence in situ hybridization or FISH).

3. Pregnancy or lactation. Women with childbearing potential who are to be collected will be advised that the marrow harvest procedure or the risk of G-CSF used for stem cell mobilization may be teratogenic and will be required to take adequate measures to prevent contraception.

4. Concurrent enrollment in any study using an investigational drug (defined as a drug not approved by the FDA) with the exception of androgens or thyroxine.

5. Physical or emotional status that would prevent compliance, ability to understand treatment plan or adequate follow-up.

6. HIV positive patients.

7. Patients with neoplastic or non-neoplastic disease of any major organ system that would compromise their ability to withstand the bone marrow harvest or apheresis procedure.

8. Patients with uncontrolled (culture or biopsy positive) infection requiring intravenous antivirals, antibiotics, or antifungals. Patients on prolonged antifungal therapy are still eligible if they are culture or biopsy negative in residual radiographic lesions, and they meet the other organ function criteria.

9. Patients unable to tolerate general anesthesia.

10. Known adverse reaction to E. coli products or G-CSF and any contraindication to leukocytosis or hypocalcemia or (where indicated) central line placement.