Pentostatin for High Risk and Refractory Chronic Graft Versus Host Disease in Children
A Phase II Study of Pentostatin For the Treatment of High Risk or Refractory Chronic GVHD in Children
1 other identifier
interventional
60
1 country
25
Brief Summary
This is a multicenter trial through the Pediatric Blood and Marrow Transplant Consortium. The Primary hypothesis of this study is that because of its effect as a potent immunosuppressive agent targeting lymphocytes, pentostatin will show a sustained response in pediatric subjects with severe chronic GVHD. Secondary hypotheses include that the infection and toxicity rate of pentostatin in this setting will be acceptable given its lack of severe myelosuppression, and subjects with refractory chronic GVHD will have significant QOL impairment and symptomatology. These may change as subjects are being treated for their chronic GVHD with pentostatin.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2004
Typical duration for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2004
CompletedFirst Submitted
Initial submission to the registry
August 31, 2005
CompletedFirst Posted
Study publicly available on registry
September 5, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2008
CompletedFebruary 3, 2009
February 1, 2009
4.6 years
August 31, 2005
February 2, 2009
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To estimate the response rate (CR and PR) of pentostatin when used to treat refractory-chronic GVHD in children.
To end of study
Secondary Outcomes (3)
To gather initial efficacy and safety data in high-risk untreated chronic GVHD in children.
To end of study
To evaluate toxicities of pentostatin when used to treat chronic GVHD in children.
To end of study
To evaluate quality of life (QOL) and symptoms at diagnosis and after therapy with pentostatin in pediatric patients with refractory chronic GVHD.
To end of study
Interventions
The drug, Pentostatin, is given every 2 weeks. This drug will be given by intravenous (IV) infusion.
Eligibility Criteria
You may qualify if:
- Allogeneic BMT or SCT recipients. Includes cord blood and peripheral blood.
- Age 0-21 years.
- FOR REFRACTORY GROUP:
- Diagnosis of chronic GVHD, confirmed by biopsy of any organ after SCT. Given the variability among centers, biopsy needs to say, at the very least, "consistent with GVHD." If there is a medical contra-indication (such as severe sclerosis with poor wound healing) or the need for an open procedure to obtain a fascial biopsy then a photograph documenting the skin and abnormal ROM studies may be submitted instead. If current GVHD represents the same episode which was previously biopsied, then a new biopsy is not necessary. If the previous biopsy was for an episode that went into remission and this is a new episode of GVHD, then a new biopsy is necessary.
- To be eligible for this portion of the study, a patient's chronic GVHD can be extensive or limited, as defined below:
- All subjects with extensive chronic GVHD are eligible. These subjects must meet the following criteria:
- Generalized skin involvement (\>50% BSA)
- OR Localized skin involvement and/or liver dysfunction plus at least one of the following:
- Liver histology showing chronic aggressive hepatitis, bridging necrosis, cirrhosis, or ductopenia.
- Eye involvement (Schirmer's test with \< 5 mm wetting)
- Involvement of minor salivary glands or oral mucosa on lip biopsy
- Involvement of any other target organs
- OR Involvement of at least 2 target organs.(Target organs are listed below under "Examples of characteristic manifestations)
- Subjects with limited chronic GVHD (defined as those with skin involvement in less than 50% BSA or isolated organ involvement 51 are also eligible. Examples of these subjects would be those with limited sclerodermatous or fascial skin disease or oral disease that is unresponsive to therapy and may be debilitating to the patient. Subjects with isolated refractory liver chronic GVHD may go on study provided they have liver histology as above.
- Examples of characteristic manifestations include:
- +19 more criteria
You may not qualify if:
- More than two previous regimens to treat chronic GVHD. A regimen for the purpose of this study is defined as an adequate trial of an immunosuppressive or immunosuppressive combination (patient was given drug or drugs for 3 months unless there was clear progression during regimen).
- Calculated Cr. Clearance\<30 ml/min/1.73m2
- Active infection not responding to oral or IV antibiotics.
- Subjects and families unwilling to firmly commit to return for follow-up doses and appointments.
- Use of any investigational agent in the past 30 days (this does not include the use of licensed agents for indications not listed in the package insert).
- Pregnancy or nursing mother; Females of child-bearing potential and sexually active males should use effective contraception while on study.
- Active veno-occlusive disease of the liver.
- Bronchiolitis obliterans (defined for the purpose of this study by respiratory symptoms such as shortness of breath or cough and FEV1\<50%).
- Karnofsky performance score less than 40 (or Lansky performance less than 40 in subjects under 16 years of age).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
Loma Linda University Medical Center
Loma Linda, California, 92350, United States
Pediatric Medical Center for Northern California
Oakland, California, 94609, United States
Nemour's Children's Clinic
Jacksonville, Florida, 32007, United States
University of Miami
Miami, Florida, 33136, United States
All Children's Health System
St. Petersburg, Florida, 33701, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
Children's Memorial Hospital
Chicago, Illinois, 60614, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
LSUHSC
New Orleans, Louisiana, 70112, United States
John's Hopkins
Baltimore, Maryland, 21287, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
St. Louis University
St Louis, Missouri, 63104, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07602, United States
Columbia Presbyterian Medical Center
New York, New York, 10032-3702, United States
New York Medical College
Valhalla, New York, 10595, United States
Rainbow Babies and Children's
Cleveland, Ohio, 44106, United States
Columbus Children's Hospital
Columbus, Ohio, 43205, United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Victor Aquino, MD
Dallas, Texas, 75390, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Southwest Texas Methodist Hospital
San Antonio, Texas, 78229, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Related Publications (1)
Jacobsohn DA, Gilman AL, Rademaker A, Browning B, Grimley M, Lehmann L, Nemecek ER, Thormann K, Schultz KR, Vogelsang GB. Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study. Blood. 2009 Nov 12;114(20):4354-60. doi: 10.1182/blood-2009-05-224840. Epub 2009 Sep 10.
PMID: 19745067DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David Jacobsohn, MD, MSc
Children's Memorial Hospital, Chicago, IL
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
August 31, 2005
First Posted
September 5, 2005
Study Start
January 1, 2004
Primary Completion
August 1, 2008
Study Completion
August 1, 2008
Last Updated
February 3, 2009
Record last verified: 2009-02