Pentostatin for High Risk and Refractory Chronic Graft Versus Host Disease in Children

Completed · Phase 2

Conditions studied: Graft vs Host Disease

In brief

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.

Key facts

Study ID

NCT00144430

Run by

Ann & Robert H Lurie Children's Hospital of Chicago

People needed

60

Starts

2004-01-01

Expected to finish

2008-08-01

Last updated by the study team

2009-02-03

Who can join

Age: 0 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

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:
• skin changes - rash, lichenoid changes, sclerodermatous changes, hypopigmentation, hyperpigmentation, loss of appendages (hair follicles, sweat glands), alopecia
• oral changes - erythema, lichenoid changes, ulceration
• hepatic involvement - obstructive jaundice, chronic hepatitis, cirrhosis
• GI involvement - nausea, vomiting, weight loss, esophageal dysmotility, malabsorption, chronic diarrhea, abdominal cramps
• sicca syndrome - dry eyes and mouth (decreased tearing, keratoconjunctivitis, oral mucosal erythema and ulcerations)
• other inflammatory conditions - myositis, arthritis, polyserositis
• To be eligible for this portion of the study subjects must have refractory disease defined below:
• Development of new sites of disease while being treated for chronic GVHD* (These criteria can be met at any time post-transplant after treatment for chronic GVHD has begun. This includes subjects who develop new sites of disease while on steroid therapy, tapering steroid therapy, or other therapy. The only necessary elements are TREATMENT of chronic GVHD and NEW area of disease. -OR-
• Progression of an initially affected site of chronic GVHD while being treated for chronic GVHD, the chronic GVHD worsens. This type of patient has worsening of any initially affected area at any time. This includes subjects that are judged to be steroid-dependent, and once a taper of steroids is initiated, they flare in the same organ. -OR-
• Failure to improve despite at least 1 month of standard therapy (These subjects have shown no response (not improved but not worse) to cGVHD therapy. These therapies include, but are not limited to:

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).

Where it is running

• Loma Linda University Medical Center — Loma Linda, California, United States
• Pediatric Medical Center for Northern California — Oakland, California, United States
• Nemour's Children's Clinic — Jacksonville, Florida, United States
• University of Miami — Miami, Florida, United States
• All Children's Health System — St. Petersburg, Florida, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Children's Memorial Hospital — Chicago, Illinois, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• LSUHSC — New Orleans, Louisiana, United States
• John's Hopkins — Baltimore, Maryland, United States
• University of Michigan — Ann Arbor, Michigan, United States
• DeVos Children's Hospital — Grand Rapids, Michigan, United States
• Children's Mercy Hospital — Kansas City, Missouri, United States
• St. Louis University — St Louis, Missouri, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Columbia Presbyterian Medical Center — New York, New York, United States
• New York Medical College — Valhalla, New York, United States
• Rainbow Babies and Children's — Cleveland, Ohio, United States
• Columbus Children's Hospital — Columbus, Ohio, United States
• Penn State Milton S. Hershey Medical Center — Hershey, Pennsylvania, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• Victor Aquino, MD — Dallas, Texas, United States
• Cook Children's Medical Center — Fort Worth, Texas, United States
• Southwest Texas Methodist Hospital — San Antonio, Texas, United States
• University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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