Reduced Intensity AlloTransplant For Osteopetrosis

NCT00638820 | Terminated Phase 2 Results DMC

• 2 other identifiers: 0704M06581MT2007-06
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination 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. The purpose of this research is to find 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.

Conditions

Osteopetrosis

Keywords

osteopetrosis

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Donor Cell Engraftment

  Number of patients with persistent presence of donor-derived cells at Day 100

  Day 100

Secondary Outcomes (3)

• Number of Patients With Transplant Related Death

  Day 100

• Number of Patients With Transplant Related Toxicity

  Day 100

• Differential Imaging and Biologic Evaluations

  Day 100, 6 months, 1, 2 and 5 years

Study Arms (1)

Intent-To-Treat

EXPERIMENTAL

Patients enrolled and received study treatment.

Procedure: Stem Cell or Umbilical Cord Blood Transplantation; Drug: Campath, Busulfan, Clofarabine; Procedure: Total Lymphoid Irradiation

Interventions

Stem Cell or Umbilical Cord Blood Transplantation PROCEDURE

Stem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42

Also known as: Bone Marrow Transplant

Intent-To-Treat

Campath, Busulfan, Clofarabine DRUG

* 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours * 11 Campath-1H 0.3 mg/kg intravenously over 2 hours * 10 Campath-1H 0.3 mg/kg intravenously over 2 hours * 9 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours * 8 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours * 7 "Rest" * 6 Clofarabine 40 mg/m2 intravenously over 2 hours * 5 Clofarabine 40 mg/m2 intravenously over 2 hours * 4 Clofarabine 40 mg/m2 intravenously over 2 hours * 3 Clofarabine 40 mg/m2 intravenously over 2 hours * 2 Clofarabine 40 mg/m2 intravenously over 2 hours

Also known as: Busulfex, Clolar,Alemtuzumab

Intent-To-Treat

Total Lymphoid Irradiation PROCEDURE

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

Also known as: Therapuetic radation, radiation therapy

Intent-To-Treat

Eligibility Criteria

• Age: Up to 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 \<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 substantially 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; Bone Marrow Transplantation; Alemtuzumab; Busulfan; Clofarabine; Radiotherapy

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; Tissue Transplantation; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Limitations and Caveats

Only 3 participants were treated in this study; all died by Day 100. Data for both treatment arms were combined due to low number. (Arm 1 utilized mobilized peripheral blood or marrow (related or unrelated). Arm 2 received cord blood transplants).

Results Point of Contact

• Title: Paul Orchard, M.D.
• 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: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 11, 2008
• First Posted: March 19, 2008
• Study Start: September 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: December 28, 2017
• Results First Posted: February 3, 2010

Record last verified: 2017-12

Locations

US (1)