AzTrials
AzTrials

Graft vs Host DiseasePhase 2NCT00144430

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

A Phase 2 study testing Pentostatin in people with Graft vs Host Disease, run by Ann & Robert H Lurie Children's Hospital of Chicago at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 1 month to 21 years
Conditions the study is for
Graft vs Host Disease
What is being tested?
Pentostatin
Type of treatment
Injection or infusion
How many people
60 participants
Where
25 sitesUnited States
Study dates
Jan 2004to Aug 2008
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
Show all 35Show fewer
  • 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:
  • Prednisone at an average of 0.5 mg/kg/day or equivalent steroid.
  • Another immunosuppressive regimen (e.g.. FK506/MMF or photopheresis).
  • FOR HIGH-RISK GROUP:
  • The vast majority of these subjects will be identified at initial diagnosis of chronic GVHD and will be subjects progressing from acute to chronic. These subjects are likely to be on steroids for acute GVHD and have skin changes that are rapidly shifting from simple erythema to a lichenoid/pebbly appearance consistent with chronic GVHD. For inclusion into this arm, the following are required:
  • Extensive skin involvement (>50%BSA) with either lichenoid or sclerodermatous changes.
  • Either one or both of the following high-risk features:
  • Thrombocytopenia (PLT<100,000)
  • Progressive onset ( i.e. Changes suggestive of progression from acute to chronic). This includes, but is not limited to, skin becoming increasingly scaly, pebbly, raised, and lymphedematous. It is not unusual to see this transition even before day 100, especially in non-myeloablative SCT and DLI. If there are any questions regarding these changes and whether they qualify, call the PI, Dr. David Jacobsohn, 773-880-3694.
  • A biopsy after SCT showing acute or chronic GVHD. A biopsy showing acute GVHD is acceptable if the clinical picture is progressing to chronic GVHD.
  • Patient is on prednisone ≥2 mg/kg/day (or equivalent dose if on another steroid) and has received more than 7 days of therapy.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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).

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • John's Hopkins

    Baltimore, Maryland, 21287

  • Children's Memorial Hospital

    Chicago, Illinois, 60614

  • Rainbow Babies and Children's

    Cleveland, Ohio, 44106

  • Columbus Children's Hospital

    Columbus, Ohio, 43205

  • Victor Aquino, MD

    Dallas, Texas, 75390

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07602

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Nemour's Children's Clinic

    Jacksonville, Florida, 32007

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Loma Linda University Medical Center

    Loma Linda, California, 92350

  • University of Miami

    Miami, Florida, 33136

  • LSUHSC

    New Orleans, Louisiana, 70112

  • Columbia Presbyterian Medical Center

    New York, New York, 10032-3702

  • Pediatric Medical Center for Northern California

    Oakland, California, 94609

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • University of Utah

    Salt Lake City, Utah, 84132

  • Southwest Texas Methodist Hospital

    San Antonio, Texas, 78229

  • St. Louis University

    St Louis, Missouri, 63104

  • All Children's Health System

    St. Petersburg, Florida, 33701

  • New York Medical College

    Valhalla, New York, 10595

Other trials in United States

About this study

Official title: A Phase II Study of Pentostatin For the Treatment of High Risk or Refractory Chronic GVHD in Children

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.

Read the detailed description

To participate in this study, subjects must have diagnosed chronic Graft versus Host Disease that is refractory to therapy or that is considered high risk (i.e. low platelet count, progressive onset and greater than 50% of body surface area affected). Subjects must have not failed more than 2 immunosuppressive regimens in order to be considered for this trial. Eligible subjects will receive intravenous pentostatin every 2 weeks for 24 weeks. If the subject has had a complete response, the therapy will end at 24 weeks. If the subject has had a partial or mixed response or stable disease, they will continue on study receiving pentostatin for 52 weeks.

Being tested
Pentostatin
Keywords
chronic graft versus host disease, graft, host, transplant, stem cell, pediatric, GVH0313, leukemia
Medical subject headings
Graft vs Host Disease, Bronchiolitis Obliterans Syndrome, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PentostatinDrug

    The drug, Pentostatin, is given every 2 weeks. This drug will be given by intravenous (IV) infusion.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To estimate the response rate (CR and PR) of pentostatin when used to treat refractory-chronic GVHD in children.

    Measured: To end of study

Secondary outcomes (3)

  1. To gather initial efficacy and safety data in high-risk untreated chronic GVHD in children.

    Measured: To end of study

  2. To evaluate toxicities of pentostatin when used to treat chronic GVHD in children.

    Measured: To end of study

  3. To evaluate quality of life (QOL) and symptoms at diagnosis and after therapy with pentostatin in pediatric patients with refractory chronic GVHD.

    Measured: To end of study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2005 (estimated)
  2. Study startJan 2004
  3. Primary completionAug 2008
  4. Study completionAug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00144430
Sponsor's protocol ID
GVH 0313
Status last verified
Feb 2009
First submitted
31 Aug 2005
Last updated
3 Feb 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19745067

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pentostatin in people with Graft vs Host Disease, run by Ann & Robert H Lurie Children's Hospital of Chicago at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To estimate the response rate (CR and PR) of pentostatin when used to treat refractory-chronic GVHD in children. (time frame: To end of study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00144430, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2009.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in