Reduced Intensity AlloTransplant For Osteopetrosis

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00638820
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arm: 1
• Duration (Months): 8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Osteopetrosis	Procedure: Stem Cell or Umbilical Cord Blood Transplantation; Drug: Campath, Busulfan, Clofarabine; Procedure: Total Lymphoid Irradiation	Phase 2

Detailed Description

This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 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, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intent-To-Treat Patients enrolled and received study treatment.

Procedure: Stem Cell or Umbilical Cord Blood Transplantation; 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; Other Names: Bone Marrow Transplant ; Drug: Campath, Busulfan, Clofarabine; 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; Other Names: Busulfex, Clolar,Alemtuzumab ; Procedure: Total Lymphoid Irradiation; Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).; Other Names: Therapuetic radation, radiation therapy

Outcome Measures

Primary Outcome Measures

1. Number of Patients Achieving Donor Cell Engraftment [Day 100]

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

Secondary Outcome Measures

1. Number of Patients With Transplant Related Death [Day 100]

   Number of participants died during study by Day 100 and reason for death was related to transplant.

2. Number of Patients With Transplant Related Toxicity [Day 100]

   Number of patients experiencing adverse effects due to transplant categorized by body system using Common Terminology Criteria for Adverse Events coding from the National Cancer Institute, Version 3.0.

3. Differential Imaging and Biologic Evaluations [Day 100, 6 months, 1, 2 and 5 years]

   These outcome measures were not assessed due to early study termination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of MInnesota, Fairview	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Paul Orchard, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00638820
• Other Study ID Numbers: 0704M06581; MT2007-06
• First Posted: Mar 19, 2008
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by , ,: osteopetrosis
• Additional relevant MeSH terms: Osteopetrosis; Busulfan; Alemtuzumab; Clofarabine

Study Results

Participant Flow

Pre-assignment Detail	This study was terminated early due to stopping rules. The first 3 patients enrolled died by Day 100 of study.

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Period Title: Overall Study
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Overall Participants	3
Age (Count of Participants)
<=18 years	2 66.7%
Between 18 and 65 years	1 33.3%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Achieving Donor Cell Engraftment
Description	Number of patients with persistent presence of donor-derived cells at Day 100
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Measure Participants	3
Number [Participants]	2 66.7%

2. Secondary Outcome

Title	Number of Patients With Transplant Related Death
Description	Number of participants died during study by Day 100 and reason for death was related to transplant.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Measure Participants	3
Number [Participants]	3 100%

3. Secondary Outcome

Title	Number of Patients With Transplant Related Toxicity
Description	Number of patients experiencing adverse effects due to transplant categorized by body system using Common Terminology Criteria for Adverse Events coding from the National Cancer Institute, Version 3.0.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Measure Participants	3
Neurologic	1 33.3%
Renal	1 33.3%
Pulmonary	3 100%
Peri-Transplant Mortality (Death by Day 100)	3 100%
Vascular	1 33.3%

4. Secondary Outcome

Title	Differential Imaging and Biologic Evaluations
Description	These outcome measures were not assessed due to early study termination.
Time Frame	Day 100, 6 months, 1, 2 and 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected from Day 1 through Day 100 of the study.
Arm/Group Title	Patients With Osteopetrosis Who Received Transplant
Arm/Group Description	All patients enrolled with osteopetrosis and received transplant.
All Cause Mortality
	Patients With Osteopetrosis Who Received Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients With Osteopetrosis Who Received Transplant
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
General disorders
Death, peri-transplant	3/3 (100%)	3
Other (Not Including Serious) Adverse Events
	Patients With Osteopetrosis Who Received Transplant
	Affected / at Risk (%)	# Events
Total	3/3 (100%)
Nervous system disorders
Neurologic	1/3 (33.3%)	1
Renal and urinary disorders
Renal	1/3 (33.3%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary	3/3 (100%)	3
Vascular disorders
Vascular	1/3 (33.3%)	1

Limitations/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).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.