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Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

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ClinicalTrials.gov Identifier: NCT00618540
Recruitment Status : Terminated (Slow accrual)
First Posted : February 20, 2008
Results First Posted : November 3, 2015
Last Update Posted : December 28, 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
Condition Histiocytosis, Langerhans-cell
Interventions Biological: alemtuzumab
Drug: fludarabine phosphate
Drug: melphalan
Procedure: stem cell transplantation
Enrollment 1
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Period Title: Overall Study
Started 1
Completed 1
Not Completed 0
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Baseline Participants 1
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants
<=18 years
1
 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 1 participants
Female
0
   0.0%
Male
1
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 1 participants
1
1.Primary Outcome
Title Overall Survival
Hide Description Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
Time Frame Year 1, Year 3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title Disease-free Survival at 12 Months Post Transplantation
Hide Description

This outcome is defined as survival with resolution of LCH at 12 months post transplant.

Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events.

Those who survive with resolution of disease are censored at the date of last contact.

Time Frame Year 1
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
3.Secondary Outcome
Title Transplantation-related Death
Hide Description Count of patients who died by day 100 related to the transplantation.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
4.Secondary Outcome
Title Neutrophil Engraftment
Hide Description Incidence of neutrophil recovery and donor chimerism at Day 100.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
1
5.Secondary Outcome
Title Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)
Hide Description The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
Time Frame Day 100 and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
1
6.Secondary Outcome
Title Incidence of Chronic GVHD
Hide Description Occurrence of symptoms in any organ system fulfilling the criteria of limited or extensive chronic GvHD (Appendix III), among patients surviving > 90 days with evidence of engraftment. Patients without chronic GvHD will be censored at time of death or last follow-up.
Time Frame Day 100 and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
7.Secondary Outcome
Title Platelet Engraftment
Hide Description Incidence of platelet recovery and donor chimerism at Day 100.
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
8.Secondary Outcome
Title Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD)
Hide Description The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
Time Frame Day 100 and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description:

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: participants
0
Time Frame The adverse event data were collected at 100 days post-transplantation.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Alemtuzumab Conditioning
Hide Arm/Group Description

Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.

alemtuzumab: Administered intravenously (IV) 0.2 mg/kg on Days -8 through -4.

fludarabine phosphate: Administered 30 mg/m2 intravenously (IV) over 30-60 min on Days -7 through -3.

(dose adjust if age <12 months)

melphalan: Administered 140 mg/m2 intravenously (IV) over 30 min on Day -2 (dose adjust if age <12 months)

stem cell transplantation: Administered as allogeneic hematopoietic, peripheral blood or umbilical cord blood transplantation

All-Cause Mortality
Alemtuzumab Conditioning
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Alemtuzumab Conditioning
Affected / at Risk (%) # Events
Total   1/1 (100.00%)    
Respiratory, thoracic and mediastinal disorders   
Respiratory syncytial virus (RSV) infection  1  1/1 (100.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Alemtuzumab Conditioning
Affected / at Risk (%) # Events
Total   1/1 (100.00%)    
Infections and infestations   
Multiple systemic infections  1  1/1 (100.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, SNOMED CT
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Angela Smith, MD
Organization: University of Minnesota, Pediatric BMT
Phone: 612-626-2778
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00618540     History of Changes
Other Study ID Numbers: 2007UC002
UMN-0612M98407 ( Other Identifier: IRB, University of Minnesota )
LCH-HCT-2006 ( Other Identifier: Histiocyte Society )
UMN-MT2006-07 ( Other Identifier: Blood and Marrow Transplantation Program )
First Submitted: February 19, 2008
First Posted: February 20, 2008
Results First Submitted: April 22, 2015
Results First Posted: November 3, 2015
Last Update Posted: December 28, 2017