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Trial record 9 of 11 for:    Mucolipidoses

Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders

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ClinicalTrials.gov Identifier: NCT01626092
Recruitment Status : Completed
First Posted : June 22, 2012
Results First Posted : October 11, 2016
Last Update Posted : December 5, 2017
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Lysosomal Storage Disease
Peroxisomal Disorder
Interventions Drug: Campath-1H
Drug: Clofarabine
Drug: Melphalan
Radiation: Total Body Irradiation with Marrow Boosting
Biological: Hematopoietic stem cell transplantation
Drug: Cyclosporine A
Drug: Mycophenolate mofetil
Enrollment 3
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Intent-To-Treat Patients
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Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,

Period Title: Overall Study
Started 3
Completed 3
Not Completed 0
Arm/Group Title Intent-To-Treat Patients
Hide Arm/Group Description

Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9

Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
<=18 years
3
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
0
   0.0%
Male
3
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants
3
1.Primary Outcome
Title Donor (Allogeneic) Hematopoietic Engraftment
Hide Description Number of patients who achieve hematopoietic engraftment - assessment of nucleated peripheral blood cells for donor (allogeneic) chimerism following this reduced-intensity HCT.
Time Frame Day 100 Following Hematopoietic Cell Transplant (HCT)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intent-To-Treat Patients
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Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,

Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: participants
1
2.Secondary Outcome
Title Transplant-Related Mortality
Hide Description Incidence of death due to complications of HCT following this reduced-intensity conditioning regimen.
Time Frame Day 100 following HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intent-To-Treat Patients
Hide Arm/Group Description:

Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,

Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title Neurologic Outcomes
Hide Description Depending upon underlying primary disease, a combination of evaluative tools (e.g. brain magnetic resonance imaging (MRI), clinical neurologic exam, neuropsychologic testing, electromyography) will be applied for assessment of neurologic function and how it may be affected by this reduced-intensity HCT regimen.
Time Frame Changes from Baseline, Days 30, 60, 100, Year 1, Year 2, Year 3 Following HCT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
None of the 3 patients enrolled in the study were evaluable for this outcome. Two had a repeat transplant and one was lost to follow-up.
Arm/Group Title Intent-To-Treat Patients
Hide Arm/Group Description:

Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intent-To-Treat Patients
Hide Arm/Group Description

Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Campath-1H: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8

Clofarabine: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9

All-Cause Mortality
Intent-To-Treat Patients
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Intent-To-Treat Patients
Affected / at Risk (%)
Total   0/3 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intent-To-Treat Patients
Affected / at Risk (%)
Total   3/3 (100.00%) 
Ear and labyrinth disorders   
Hearing loss  1/3 (33.33%) 
Eye disorders   
Decreased vision  2/3 (66.67%) 
Gastrointestinal disorders   
Abdominal pain  1/3 (33.33%) 
Nausea  3/3 (100.00%) 
Vomiting  2/3 (66.67%) 
Mucositis  3/3 (100.00%) 
Acid reflux  1/3 (33.33%) 
Loose stools  1/3 (33.33%) 
General disorders   
Fever  2/3 (66.67%) 
Infections and infestations   
Positive blood culture - Staphylococcus aureus  1/3 (33.33%) 
Positive blood culture - Escherichia coli  1/3 (33.33%) 
Fever  1/3 (33.33%) 
BK viruria  1/3 (33.33%) 
Adenoviremia  1/3 (33.33%) 
Injury, poisoning and procedural complications   
Acute radiation syndrome  1/3 (33.33%) 
Graft failure  3/3 (100.00%) 
Investigations   
Elevated lipase  1/3 (33.33%) 
Serum amylase increased  2/3 (66.67%) 
Hypogammaglobulinemia  1/3 (33.33%) 
Elevated ALT  1/3 (33.33%) 
Elevated AST  1/3 (33.33%) 
Metabolism and nutrition disorders   
Anorexia  2/3 (66.67%) 
Nervous system disorders   
Dizziness  1/3 (33.33%) 
Muscle spasms  1/3 (33.33%) 
Headache  1/3 (33.33%) 
Psychiatric disorders   
Anxiety  2/3 (66.67%) 
Agitation  1/3 (33.33%) 
Renal and urinary disorders   
Dysuria  1/3 (33.33%) 
Respiratory, thoracic and mediastinal disorders   
Decreased oxygen saturation  1/3 (33.33%) 
Skin and subcutaneous tissue disorders   
Rash  1/3 (33.33%) 
Vascular disorders   
Hypertension  3/3 (100.00%) 
Hypotension  1/3 (33.33%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Weston P Miller, MD
Organization: Masonic Cancer Center, University of Minnesota
Phone: 612-626-2778
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01626092     History of Changes
Other Study ID Numbers: 2011LS147
MT2011-24 ( Other Identifier: Blood and Marrow Transplantation Program )
First Submitted: June 20, 2012
First Posted: June 22, 2012
Results First Submitted: August 17, 2016
Results First Posted: October 11, 2016
Last Update Posted: December 5, 2017