Allogeneic Transplantation For Severe Osteopetrosis

University of Minnesota (UMN)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Severe Osteopetrosis

Treatments: Drug: Fludarabine monophosphate; Drug: Campath-1H; Drug: Busulfan; Drug: Cyclophosphamide; Radiation: Total Lymphoid Irradiation; Procedure: marrow graft transplantation; Procedure: umbilical cord blood transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT00775931

0808M42261 (Other Identifier)

MT2008-20

Details and patient eligibility

About

The purpose of this research is to explore what we believe may be a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors.

Full description

This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Enrollment: 7 patients

Sex: All

Ages: 1 day to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.

  1. Bones that are uniformly markedly dense based on skeletal survey
  2. No history that would suggest autosomal dominant inheritance
  3. Evidence of hematologic changes that are attributed to the underlying disease, including

• the need for ongoing transfusions, OR

• the presence of progressive anemia or thrombocytopenia, OR

• a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR

• persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.

Exclusion criteria

• Patients >45 years of age
• Evidence of hepatic failure
• Pulmonary dysfunction sufficient to significantly increase the risk of transplant.
• Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
• Cardiac compromise sufficient to substantially increase the risk of transplantation
• Severe, stable neurologic impairment.
• Human immunodeficiency virus (HIV) positivity.
• Pregnant or lactating females

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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7 participants in 2 patient groups

marrow graft transplant conditioning

Active Comparator group

Description:

Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.

Treatment:

Procedure: marrow graft transplantation

Radiation: Total Lymphoid Irradiation

Drug: Campath-1H

Drug: Busulfan

Drug: Fludarabine monophosphate

cord blood transplant conditioning

Active Comparator group

Description:

Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.

Treatment:

Procedure: umbilical cord blood transplantation

Drug: Cyclophosphamide

Drug: Campath-1H

Drug: Busulfan