Allogeneic Transplantation For Severe Osteopetrosis

NCT00775931 | Completed Phase 2 Results DMC

• 2 other identifiers: MT2008-200808M42261
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Severe Osteopetrosis

Keywords

osteopetrosis

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Achieved Donor Cell Engraftment

  Day 100

Secondary Outcomes (3)

• Transplant Related Mortality at 100 Days

  day 100

• Transplant Related Toxicity

  Day 100 post transplant

• Incidence of Grade II - IV Acute Graft-versus-host Disease

  by Day 100 after transplant

Study Arms (2)

marrow graft transplant conditioning

ACTIVE COMPARATOR

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.

Drug: Campath-1H; Radiation: Total Lymphoid Irradiation; Drug: Busulfan; Drug: Fludarabine monophosphate; Procedure: marrow graft transplantation

cord blood transplant conditioning

ACTIVE COMPARATOR

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.

Procedure: umbilical cord blood transplantation; Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan

Interventions

umbilical cord blood transplantation PROCEDURE

Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.

Also known as: UCBT

cord blood transplant conditioning

Campath-1H DRUG

Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.

Also known as: Alemtuzumab

cord blood transplant conditioning; marrow graft transplant conditioning

Total Lymphoid Irradiation RADIATION

Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).

Also known as: TLI

marrow graft transplant conditioning

Cyclophosphamide DRUG

Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.

Also known as: Cytoxan

cord blood transplant conditioning

Busulfan DRUG

patients\<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients \>12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.

Also known as: Busulfex

cord blood transplant conditioning; marrow graft transplant conditioning

Fludarabine monophosphate DRUG

Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.

Also known as: Fludara

marrow graft transplant conditioning

marrow graft transplantation PROCEDURE

Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.

Also known as: HSCT

marrow graft transplant conditioning

Eligibility Criteria

• Age: 1 Day - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Bones that are uniformly markedly dense based on skeletal survey
• No history that would suggest autosomal dominant inheritance
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of MInnesota, Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Osteopetrosis

Interventions

Cord Blood Stem Cell Transplantation; Alemtuzumab; Cyclophosphamide; Busulfan; fludarabine phosphate

Condition Hierarchy (Ancestors)

Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

Because the disease being treated on this study is rare, our intent was to only report these outcomes in context with other protocols. At some point in the future if we have enough patients we will analyze the data.

Results Point of Contact

• Title: Dr. Paul Orchard
• Organization: Masonic Cancer Center, University of Minnesota

orcha001@umn.edu

612-626-2313

Study Officials

• Paul Orchard, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2008
• First Posted: October 20, 2008
• Study Start: August 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 31, 2019
• Results First Posted: July 31, 2019

Record last verified: 2019-07

Locations

US (1)