Trial Outcomes & Findings for Allogeneic Transplantation For Severe Osteopetrosis (NCT NCT00775931)

NCT ID: NCT00775931

Last Updated: 2019-07-31

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

7 participants

Primary outcome timeframe

Day 100

Results posted on

2019-07-31

Participant Flow

Participant milestones

Participant milestones
Measure
Marrow Graft Transplant Conditioning
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Overall Study
STARTED
6
1
Overall Study
COMPLETED
6
1
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Allogeneic Transplantation For Severe Osteopetrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Marrow Graft Transplant Conditioning
n=6 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Total
n=7 Participants
Total of all reporting groups
Age, Categorical
<=18 years
4 Participants
n=5 Participants
0 Participants
n=7 Participants
4 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
1 Participants
n=7 Participants
5 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 100

Outcome measures

Outcome measures
Measure
Marrow Graft Transplant Conditioning
n=6 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Number of Patients Who Achieved Donor Cell Engraftment
5 Participants
0 Participants

SECONDARY outcome

Timeframe: day 100

Outcome measures

Outcome measures
Measure
Marrow Graft Transplant Conditioning
n=6 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Transplant Related Mortality at 100 Days
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 100 post transplant

Outcome measures

Outcome measures
Measure
Marrow Graft Transplant Conditioning
n=6 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Transplant Related Toxicity
3 Participants
1 Participants

SECONDARY outcome

Timeframe: by Day 100 after transplant

Outcome measures

Outcome measures
Measure
Marrow Graft Transplant Conditioning
n=6 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 Participants
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Incidence of Grade II - IV Acute Graft-versus-host Disease
2 Participants
0 Participants

Adverse Events

Marrow Graft Transplant Conditioning

Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths

Cord Blood Transplant Conditioning

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Marrow Graft Transplant Conditioning
n=6 participants at risk
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 participants at risk
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
General disorders
Multi-Organ Failure
16.7%
1/6
0.00%
0/1
Cardiac disorders
Myocarditis
16.7%
1/6
0.00%
0/1
General disorders
Acute Graft versus Host Disease
16.7%
1/6
0.00%
0/1

Other adverse events

Other adverse events
Measure
Marrow Graft Transplant Conditioning
n=6 participants at risk
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Total Lymphoid Irradiation: Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA). Busulfan: 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. Fludarabine monophosphate: 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.
Cord Blood Transplant Conditioning
n=1 participants at risk
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. Campath-1H: Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19. Busulfan: 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. Cyclophosphamide: 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
Nervous system disorders
Posterior Reversible Encephalopathy Syndrome
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Pulmonary Hemorrhage
16.7%
1/6
100.0%
1/1
Respiratory, thoracic and mediastinal disorders
Pulmonary Hypertension
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Reactive Airway Disease
16.7%
1/6
0.00%
0/1
Renal and urinary disorders
Renal Failure
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
33.3%
2/6
0.00%
0/1
Nervous system disorders
Seizure
16.7%
1/6
0.00%
0/1
Gastrointestinal disorders
Small Bowel Ascites
0.00%
0/6
100.0%
1/1
Eye disorders
Subconjunctival Hemorrhages
16.7%
1/6
0.00%
0/1
Infections and infestations
Upper Respiratory Infection
16.7%
1/6
0.00%
0/1
Infections and infestations
Viral Infection, Blood
33.3%
2/6
100.0%
1/1
Infections and infestations
Viral Infection, Myocardium
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
33.3%
2/6
0.00%
0/1
Infections and infestations
Acute Sinusitis
0.00%
0/6
100.0%
1/1
Respiratory, thoracic and mediastinal disorders
Atelectasis
0.00%
0/6
100.0%
1/1
Blood and lymphatic system disorders
Autoimmune Hemolytic Anemia
16.7%
1/6
0.00%
0/1
Infections and infestations
Bacterial Infection, Blood
66.7%
4/6
0.00%
0/1
Infections and infestations
Bacterial Infection, Respiratory
16.7%
1/6
100.0%
1/1
Infections and infestations
Bacterial Infection, Feces
16.7%
1/6
100.0%
1/1
Vascular disorders
Capillary Leak
16.7%
1/6
0.00%
0/1
Blood and lymphatic system disorders
Blood Clot in Bladder Wall
0.00%
0/6
100.0%
1/1
Renal and urinary disorders
Requires Continuous Veno-Venous Hemofiltration, NOS
16.7%
1/6
0.00%
0/1
Infections and infestations
Cystitis
33.3%
2/6
0.00%
0/1
Cardiac disorders
Complete Heart Block
16.7%
1/6
0.00%
0/1
Infections and infestations
Fungal Infection, Blood
33.3%
2/6
0.00%
0/1
Infections and infestations
Fungal Infection, Respiratory
50.0%
3/6
100.0%
1/1
Infections and infestations
Fungal Infection, Feces
0.00%
0/6
100.0%
1/1
Infections and infestations
Fungal Infection, Urine
16.7%
1/6
0.00%
0/1
Nervous system disorders
Further Decompression of Lateral and Third Ventricles
16.7%
1/6
0.00%
0/1
Renal and urinary disorders
Requires Hemodialysis, NOS
16.7%
1/6
100.0%
1/1
Vascular disorders
Hypertension
16.7%
1/6
0.00%
0/1
Renal and urinary disorders
Hyperechogenic Renomegaly with Ascites
0.00%
0/6
100.0%
1/1
Metabolism and nutrition disorders
Hyperglycemia
16.7%
1/6
0.00%
0/1
Nervous system disorders
Intracranial Hemorrhage
16.7%
1/6
0.00%
0/1
Nervous system disorders
Intraparenchymal Bleed
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Requires Intubation, NOS
83.3%
5/6
100.0%
1/1
Blood and lymphatic system disorders
Large Splenic Infarct
0.00%
0/6
100.0%
1/1
Infections and infestations
Sinus Infection
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Low Lung Volumes
0.00%
0/6
100.0%
1/1
Vascular disorders
Obstruction of Left Proximal Internal Jugular Vein
16.7%
1/6
0.00%
0/1
Eye disorders
Papilledema and Retinal Hemorrhages Leading to Blindness
16.7%
1/6
0.00%
0/1
Gastrointestinal disorders
Partial Small Bowel Obstruction
16.7%
1/6
0.00%
0/1
Cardiac disorders
Pericardial Effusion
83.3%
5/6
100.0%
1/1
Cardiac disorders
Placement of Epicardial Ventricular Pacing Wire
16.7%
1/6
0.00%
0/1
Respiratory, thoracic and mediastinal disorders
Pneumonia
83.3%
5/6
100.0%
1/1

Additional Information

Dr. Paul Orchard

Masonic Cancer Center, University of Minnesota

Phone: 612-626-2313

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place