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

• 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: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

• Study Type: Interventional
• Study Design: Allocation: N/A; 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

Participant Flow

Recruitment Details
Pre-assignment Details

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

Baseline Characteristics

Arm/Group Title		Intent-To-Treat Patients
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
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

Outcome Measures

1. Primary Outcome

Title	Donor (Allogeneic) Hematopoietic Engraftment
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intent-To-Treat Patients
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
	1

2. Secondary Outcome

Title	Transplant-Related Mortality
Description	Incidence of death due to complications of HCT following this reduced-intensity conditioning regimen.
Time Frame	Day 100 following HCT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intent-To-Treat Patients
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
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

Outcome Measure Data

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
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.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Intent-To-Treat Patients
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	--/--
Serious Adverse Events
	Intent-To-Treat Patients
	Affected / at Risk (%)
Total	0/3 (0.00%)
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%)

Limitations and Caveats

[Not Specified]

More Information

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
• EMail: mill4991@umn.edu

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT01626092
• 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