Sclerotic Graft Versus Host DiseasePhase 2NCT00702689
Imatinib Mesylate to Treat Skin Changes in Patients With Chronic Graft-Versus-Host Disease
A Phase 2 study testing Gleevec, STI571(Imatinib Mesylate) in people with Sclerotic Graft Versus Host Disease and Imatinib Mesylate, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant, resulting from the donor's immune cells attacking the cells of the body of the recipient. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Sclerotic Graft Versus Host Disease, Imatinib Mesylate
- What is being tested?
- Gleevec, STI571(Imatinib Mesylate)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2008to 26 Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Sclerodermatous graft versus host disease (ScGVHD) manifesting after at least 100 days following allogeneic hematopoietic stem cell transplantation is considered diagnostic for chronic graft versus host disease (cGVHD) according to National Institutes of Health (NIH) cGVHD Consensus Statement diagnostic criteria.
- This diagnosis can be made clinically or by histopathology. The diagnosis must be confirmed by the principal investigator (PI), or lead associate investigator (LAI).
- Skin biopsies will be reviewed by the National Cancer Institute (NCI) Laboratory of Pathology to confirm the diagnosis of ScGVHD.
- Patients must have measurable limitation in range of motion, defined as ScGVHD with or without fasciitis, restricting range of motion (ROM) of at least one joint with a minimum deficit of 25 percent.
- Prior therapy: Patients must have cGVHD refractory to at least one treatment regimen for cGVHD.
- One prior regimen must have included systemic corticosteroids at the equivalent prednisone dosing of 1mg/kg/day times 14 days.
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- Patients in whom calcineurin inhibitors or corticosteroids are medically contraindicated may also be eligible for enrollment.
- Patients who have had stabilization of disease on calcineurin inhibitors or steroids, but in whom these medications cannot be tapered without disease flare are also eligible.
- Patient must be on stable or tapering immunosuppressive regimen for at least one month.
- Age: 4 years of age or older at the time of enrollment. Lower age limit set by lower established age limit norms of ROM scores for measurement criteria.
- Life expectancy of greater than 6 months.
- Karnofsky greater than or equal to 60 percent.
- Patients must be platelet transfusion and growth factor independent at the time of study entry.
- Patients must have adequate organ and marrow function as defined below. Patients with Gilbert syndrome are excluded from the requirement of a normal bilirubin.
- (Gilbert syndrome is found in 3-10 percent of the general population, and is characterized by mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis).
- absolute neutrophil count greater than or equal to 1,000/mcL
- platelets greater than or equal to 50,000/mcL
- total bilirubin less than 3 times upper limit of normal
- aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)serum glutamic pyruvic transaminase (SGPT) less than 5 times upper limit of normal
- creatinine age-adjusted within normal limits
- OR
- creatinine clearance greater than 20mL/min/1.73 m^2 for adults and pediatric patients with body surface area (BSA) greater than 0.97 m^2 with creatinine levels above institutional normals and greater than or equal to 40 mL/min 1.73 m^2 for pediatric patients with BSA less than 0.97 m^2.
- Age less than 5 years old Maximum Serum Creatinine 0.8 mg/dL
- Age 5 or less than 10 years old Maximum Serum Creatinine 1.0 mg/dL
- Age 10 or less than 15 years old Maximum Serum Creatinine 1.2 mg/dL
- Age 15 years old or greater Maximum Serum Creatinine 1.5 mg/dL
- Normal cardiac function for age as determined by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) (normal left ventricular (LV) function as measured by ejection fraction or shortening fraction).
- The effects of imatinib mesylate on the developing human fetus at the recommended therapeutic dose are unknown.
- For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for six months following completion of therapy.
- Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- All patients or their legal guardian (for patients less than 18 years old) must sign an institutional review board (IRB) approved document of informed consent (chronic graft versus host disease (cGVHD) natural history or any National Cancer Institute (NCI) protocol allowing for screening procedures) prior to performing studies to determine patient eligibility.
- After confirmation of patient eligibility all patients or their legal guardian must sign the protocol-specific informed consent.
- Pediatric patients will be included in age appropriate discussions and age appropriate assent will be obtained in accordance with National Institutes of Health (NIH) guidelines.
- Durable Power of Attorney (DPA): All patients 18 years of age at the time of enrollment will be offered the opportunity to assign DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
Who cannot join
- Patients who have had chemotherapy, radiotherapy, or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents, including extracorporeal photopheresis.
- Patients may not have received monoclonal antibody therapy within 6 weeks.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib mesylate.
- Patients receiving any of the following medications or substances that are inhibitors or inducers of P450 3A4 are ineligible.
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- Use of the following medications must be discontinued at least two weeks prior to starting therapy:
- Alfuzosin
- Aprepitant
- Carbamazepine
- Clarithromycin
- Eletriptan
- Erythromycin
- Pimozide
- St John's Wort
- Warfarin
- A list of medications and substances known or with the potential to interact with the P450 3A4 isoenzyme is provided in Section 8.
- Imatinib mesylate is likely to increase the blood level of drugs that are substrates of CYP2C9, CYP2D6 and CYP3A4/5.
- Close monitoring is warranted when using agents metabolized by these enzymes. Grapefruit juice should not be consumed while on therapy.
- Prior treatment with imatinib mesylate or other tyrosine kinase inhibitor after the date of transplant.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary, hepatic, or other organ dysfunction, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the patient's ability to tolerate protocol therapy.
- Pregnant women are excluded from this study because imatinib mesylate is an agent with the potential for teratogenic or abortifacient effects.
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with imatinib mesylate, breastfeeding should be discontinued if the mother is treated with imatinib mesylate.
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with imatinib mesylate and the possibility of associated severe immunosuppression.
- Patients with active hepatitis C or hepatitis B infection as defined by seropositivity for hepatitis C or hepatitis B (HepBSAg) and elevated transaminases, as GVHD manifestations involving the liver will be indistinguishable and drug-toxicity uninterpretable.
- Persistent malignancy, requiring ongoing therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of Imatinib Mesylate in Children and Adults With Sclerotic Skin Changes of Chronic Graft-Versus-Host Disease
Background:
Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant, resulting from the donor's immune cells attacking the cells of the body of the recipient. One effect of GVHD is fibrosis (scarring) of the skin that can lead to impaired function, decreased quality of life and increased risk of death. This is known as sclerotic skin changes of GVHD, or sclerodermatous graft versus host disease (ScGVHD).
Read more
Imatinib mesylate (Gleevec) is a drug that has been approved by the Food and Drug Administration to treat cancer in humans and fibrosing conditions in animals.
Objectives:
To see if imatinib mesylate can improve ScGVHD and evaluate its effect on other GVHD symptoms
To assess the side effects of imatinib mesylate in patients with GVHD
To evaluate blood, body fluids and tissue samples in patients to try to better understand the biology of ScGVHD
Eligibility:
Patients 4 years of age and older with ScGVHD
Design:
Initial treatment: Participants take imatinib mesylate tablets once a day for up to 6 months, as long as their GVHD does not get worse and they do not develop unacceptable side effects of the drug.
Evaluations: Participants are evaluated at 1, 3 and 6 months at the National Institutes of Health (NIH) Clinical Center with procedures that may include the following:
Medical history and physical examination
Blood and urine tests
Lung function test
Skin biopsy
Magnetic resonance imaging (MRI) scan
Specialty consultations (e.g., physical or rehabilitative therapy, dentist, eye doctor, dermatologist)
Electrocardiogram (EKG)
Echocardiogram (ultrasound test of the heart)
Muga scan (nuclear medicine test of the heart)
Quality-of-life questionnaires
Apheresis (procedure for collecting quantities of white blood cells)
Office visits with local physician once a week for 1 month, then once every 2 weeks for 5 months
Followup visits at National Institutes of Health (NIH) every 6 months for 1 year
Continuing treatment: Patients who improve continue to receive imatinib mesylate for up to 6 months after their best response and are followed for up to 2 years. Patients who continue to respond or who become worse after stopping treatment may receive additional treatment for up to 2 years.
Read the detailed description
Background:
Chronic graft versus host disease (cGVHD) is a major complication of allogeneic stem cell transplant (alloHSCT). The sclerotic skin manifestations of chronic cutaneous GVHD (ScGVHD) can lead to significant functional impairment and no satisfactory therapy exists to adequately treat this form of cGVHD.
Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor with potent activity against platelet derived growth factor receptor (PDGFR) signaling, a key cytokine pathway which has been implicated in fibrotic disease in general, and in extensive cGVHD in particular.
We hypothesize that treatment with imatinib mesylate will reduce the sclerotic manifestations of cGVHD as assessed by quantitative range of motion assessment of an affected joint.
Objectives:
Primary Objective:
To investigate whether imatinib mesylate results in clinical improvement in skin fibrosis in children and adults with ScGVHD using range of motion assessment of affected joints.
To determine if imatinib mesylate 200 mg daily is tolerated by patients with cGVHD.
Secondary Objectives:
To assess toxicity associated with imatinib mesylate in patients with cGVHD.
To establish outcome criteria for the evaluation of ScGVHD using multi-modality objective and subjective assessments, including magnetic resonance imaging, skin scoring, and patient self-reported measures.
To evaluate biomarkers of disease activity and correlative response measures to treatment with imatinib mesylate.
To assess quality of life and functional measures of disease activity and to evaluate changes through the course of therapy.
To evaluate the response of other organ manifestations affected by cGVHD to treatment with imatinib mesylate.
To evaluate steady-state pharmacokinetics of imatinib mesylate in the cGVHD patient population.
Eligibility:
Patients age 4 years of age or older with the diagnosis of ScGVHD.
Design:
This is an open-label, pilot study of imatinib mesylate.
Treatment cycles are 28-day cycles with no rest period between cycles.
A target of 10 evaluable patients will be enrolled on this trial.
- Being tested
- Gleevec, STI571(Imatinib Mesylate)
- Keywords
- Skin Sclerosis, Graft Versus Host Disease
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gleevec, STI571(Imatinib Mesylate)Drug
Also called Gleevec, ST1571
Cohort 1 - Pts 1-8:Adults: 400mg imatinib mesylate daily; Children: 260mg/m^2 daily (400mg maximum), followed by dose de-escalation for adverse events.
Cohort 2 - Pts 9-20:Adults - 100 mg oral dose daily (increase to 200 mg daily after 28 days if well tolerated). Children - 65 mg/m^2 oral dose daily (increase to 130 mg/m^2 daily after 28 days if well tolerated)
| Study group | Role | What they receive |
|---|---|---|
| Imatinib mesylate in patients with cGVHD | Experimental | Cohort 1 - Pts 1-8:Adults: 400mg imatinib mesylate daily; Children: 260mg/m^2 daily (400mg maximum), followed by dose de-escalation for adverse events.
Cohort 2 - Pts 9-20:Adults - 100 mg oral dose daily (increase to 200 mg daily after 28 days if well tolerated). Children - 65 mg/m^2 oral dose daily (increase to 130 mg/m^2 daily after 28 days if well tolerated) Receives: Drug: Gleevec, STI571(Imatinib Mesylate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months
A change in ROM is 25% or greater from baseline. A partial response required improvement in 25% or more in ROM. Progression required 25% or greater loss of ROM.Patients with negative values in the Table are those who lost ROM. Percent improvement in ROM for 1-3 target joints. For patients with >1 target joint, the average ROM improvement was calculated. The average percentage change in ROM deficit from baseline to 6 months was obtained based on the number of degrees of ROM change (6 months)/total ROM deficit (baseline) at each joint.
Measured: 6 months
Primary Range of Motion (ROM) Response
Progressive disease is defined as joint ROM: decrease of >25% in composite ROM score on 2 consecutive evaluations at least 2 weeks apart, but not greater than 4 weeks apart or steroid pulse: >1 steroid pulse per 3 month period if administered for sclerotic-type chronic graft versus host disease (ScGVHD). Response is joint ROM: increase of >25% in composite ROM score. Maximal response is a response with no further improvement over 2 sequential 3-month evaluations. Stable disease does not meet the criteria for progression, response, or maximal response.
Measured: 6 months
Secondary outcomes (6)
Number of Participants With Adverse Events
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: Date treatment consent signed to date off study, approximately, 41 months, 27 days
Average Percentage Change in Range of Motion (ROM) Deficit
One or more joints were assessed for ROM deficit by a physiatrist with expertise in graft versus host disease and joint ROM.
Measured: 6 months
Total Skin Score at Baseline and 6 Months
Total skin score was graded by the National Institutes of Health Consensus Criteria. Skin score was calculated by dividing the total score by seven domains (skin, eye, oral, joint, gastrointestinal, hepatic, pulmonary) in men and 8 domains in women (previous domains noted plus gynecologic). Total skin score is a percentage of body surface area (BSA) involvement (range 0-100%). It was calculated from the sum of moveable body surface BSA and non-moveable BSA. Higher numbers = greater body surface area affected.
Measured: Baseline and 6 Months
Total Chronic Graft Versus Host Disease (cGVHD) Provider Global Rating Score at Baseline and 6 Months
The provider global rating is a physician impression of severity of cGVHD symptoms from a scale of zero (no symptoms) to 10 (most severe GVHD symptoms possible).
Measured: Baseline and 6 months
Lung Function Score at Baseline and 6 Months
Lung function was graded by the National Institutes of Health Chronic Graft Versus Host Disease organ response criteria. The Lung function score = forced expiratory volume 1 (FEV1) score + carbon monoxide diffusing capacity (DLCO) score, with a possible range of 2 (better outcome)-12 (worst outcome). The percent predicted FEV1 and DLCO (adjusted for hematocrit but not alveolar volume) should be converted to a numeric score as follows: >80% =1; 70-79% = 2; 60-69% = 3; 50-59% = 4; 40-49% = 5; <40% = 6.
Measured: Baseline and 6 Months
Change in Immunosuppression
Change in immunosuppression was defined by an increase or decrease in steroid use form baseline.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2008 (estimated)
- Study start15 Dec 2008
- Primary completion18 May 2011
- Study completion26 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Sclerotic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Edward Cowen, M.D., National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Investigators
- Edward W Cowen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00702689
- Sponsor's protocol ID
- 080148
- Other IDs
- 08-AR-0148
- Status last verified
- Mar 2020
- First submitted
- 19 Jun 2008
- Last updated
- 30 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baird K, Comis LE, Joe GO, Steinberg SM, Hakim FT, Rose JJ, Mitchell SA, Pavletic SZ, Figg WD, Yao L, Flanders KC, Takebe N, Sarantopoulos S, Booher S, Cowen EW. Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Jun;21(6):1083-90. doi: 10.1016/j.bbmt.2015.03.006. Epub 2015 Mar 12.
PubMed 25771402Rosenthal EA, Ho PS, Joe GO, Mitchell SA, Booher S, Pavletic SZ, Baird K, Cowen EW, Comis LE. Motor ability, function, and health-related quality of life as correlates of symptom burden in patients with sclerotic chronic graft-versus-host disease receiving imatinib mesylate. Support Care Cancer. 2020 Aug;28(8):3679-3689. doi: 10.1007/s00520-019-05207-z. Epub 2019 Dec 6.
PubMed 31811481
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Imatinib Mesylate in Children and Adults With Sclerotic Skin Changes of Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT00702689
- Acronym / sponsor ID
- 080148
- Keywords
- Skin Sclerosis, Graft Versus Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Dec 2008 (actual)
- Primary completion
- 18 May 2011 (actual)
- Study completion
- 26 Feb 2020 (actual)
- First posted
- 20 Jun 2008 (estimated)
- Results
- Posted 19 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant, resulting from the donor's immune cells attacking the cells of the body of the recipient. One effect of GVHD is fibrosis (scarring) of the skin that can lead to impaired function, decreased quality of life and increased risk of death. This is known as sclerotic skin changes of GVHD, or sclerodermatous graft versus host disease (ScGVHD).
Imatinib mesylate (Gleevec) is a drug that has been approved by the Food and Drug Administration to treat cancer in humans and fibrosing conditions in animals.
Objectives:
To see if imatinib mesylate can improve ScGVHD and evaluate its effect on other GVHD symptoms
To assess the side effects of imatinib mesylate in patients with GVHD
To evaluate blood, body fluids and tissue samples in patients to try to better understand the biology of ScGVHD
Eligibility:
Patients 4 years of age and older with ScGVHD
Design:
Initial treatment: Participants take imatinib mesylate tablets once a day for up to 6 months, as long as their GVHD does not get worse and they do not develop unacceptable side effects of the drug.
Evaluations: Participants are evaluated at 1, 3 and 6 months at the National Institutes of Health (NIH) Clinical Center with procedures that may include the following:
Medical history and physical examination
Blood and urine tests
Lung function test
Skin biopsy
Magnetic resonance imaging (MRI) scan
Specialty consultations (e.g., physical or rehabilitative therapy, dentist, eye doctor, dermatologist)
Electrocardiogram (EKG)
Echocardiogram (ultrasound test of the heart)
Muga scan (nuclear medicine test of the heart)
Quality-of-life questionnaires
Apheresis (procedure for collecting quantities of white blood cells)
Office visits with local physician once a week for 1 month, then once every 2 weeks for 5 months
Followup visits at National Institutes of Health (NIH) every 6 months for 1 year
Continuing treatment: Patients who improve continue to receive imatinib mesylate for up to 6 months after their best response and are followed for up to 2 years. Patients who continue to respond or who become worse after stopping treatment may receive additional treatment for up to 2 years.
Detailed description
Background:
Chronic graft versus host disease (cGVHD) is a major complication of allogeneic stem cell transplant (alloHSCT). The sclerotic skin manifestations of chronic cutaneous GVHD (ScGVHD) can lead to significant functional impairment and no satisfactory therapy exists to adequately treat this form of cGVHD.
Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor with potent activity against platelet derived growth factor receptor (PDGFR) signaling, a key cytokine pathway which has been implicated in fibrotic disease in general, and in extensive cGVHD in particular.
We hypothesize that treatment with imatinib mesylate will reduce the sclerotic manifestations of cGVHD as assessed by quantitative range of motion assessment of an affected joint.
Objectives:
Primary Objective:
To investigate whether imatinib mesylate results in clinical improvement in skin fibrosis in children and adults with ScGVHD using range of motion assessment of affected joints.
To determine if imatinib mesylate 200 mg daily is tolerated by patients with cGVHD.
Secondary Objectives:
To assess toxicity associated with imatinib mesylate in patients with cGVHD.
To establish outcome criteria for the evaluation of ScGVHD using multi-modality objective and subjective assessments, including magnetic resonance imaging, skin scoring, and patient self-reported measures.
To evaluate biomarkers of disease activity and correlative response measures to treatment with imatinib mesylate.
To assess quality of life and functional measures of disease activity and to evaluate changes through the course of therapy.
To evaluate the response of other organ manifestations affected by cGVHD to treatment with imatinib mesylate.
To evaluate steady-state pharmacokinetics of imatinib mesylate in the cGVHD patient population.
Eligibility:
Patients age 4 years of age or older with the diagnosis of ScGVHD.
Design:
This is an open-label, pilot study of imatinib mesylate.
Treatment cycles are 28-day cycles with no rest period between cycles.
A target of 10 evaluable patients will be enrolled on this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib mesylate in patients with cGVHD | Experimental | Drug: Gleevec, STI571(Imatinib Mesylate)Cohort 1 - Pts 1-8:Adults: 400mg imatinib mesylate daily; Children: 260mg/m^2 daily (400mg maximum), followed by dose de-escalation for adverse events. Cohort 2 - Pts 9-20:Adults - 100 mg oral dose daily (increase to 200 mg daily after 28 days if well tolerated). Children - 65 mg/m^2 oral dose daily (increase to 130 mg/m^2 daily after 28 days if well tolerated) |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (35 listed)
- Sclerodermatous graft versus host disease (ScGVHD) manifesting after at least 100 days following allogeneic hematopoietic stem cell transplantation is considered diagnostic for chronic graft versus host disease (cGVHD) according to National Institutes of Health (NIH) cGVHD Consensus Statement diagnostic criteria.
- This diagnosis can be made clinically or by histopathology. The diagnosis must be confirmed by the principal investigator (PI), or lead associate investigator (LAI).
- Skin biopsies will be reviewed by the National Cancer Institute (NCI) Laboratory of Pathology to confirm the diagnosis of ScGVHD.
- Patients must have measurable limitation in range of motion, defined as ScGVHD with or without fasciitis, restricting range of motion (ROM) of at least one joint with a minimum deficit of 25 percent.
- Prior therapy: Patients must have cGVHD refractory to at least one treatment regimen for cGVHD.
Key exclusion criteria (26 listed)
- Patients who have had chemotherapy, radiotherapy, or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents, including extracorporeal photopheresis.
- Patients may not have received monoclonal antibody therapy within 6 weeks.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib mesylate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gleevec, STI571(Imatinib Mesylate)Also: Gleevec, ST1571Cohort 1 - Pts 1-8:Adults: 400mg imatinib mesylate daily; Children: 260mg/m^2 daily (400mg maximum), followed by dose de-escalation for adverse events. Cohort 2 - Pts 9-20:Adults - 100 mg oral dose daily (increase to 200 mg daily after 28 days if well tolerated). Children - 65 mg/m^2 oral dose daily (increase to 130 mg/m^2 daily after 28 days if well tolerated) | Drug | Imatinib mesylate in patients with cGVHD |
Primary outcome
Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months
Time frame: 6 months
A change in ROM is 25% or greater from baseline. A partial response required improvement in 25% or more in ROM. Progression required 25% or greater loss of ROM.Patients with negative values in the Table are those who lost ROM. Percent improvement in ROM for 1-3 target joints. For patients with >1 target joint, the average ROM improvement was calculated. The average percentage change in ROM deficit from baseline to 6 months was obtained based on the number of degrees of ROM change (6 months)/total ROM deficit (baseline) at each joint.
Primary Range of Motion (ROM) Response
Time frame: 6 months
Progressive disease is defined as joint ROM: decrease of >25% in composite ROM score on 2 consecutive evaluations at least 2 weeks apart, but not greater than 4 weeks apart or steroid pulse: >1 steroid pulse per 3 month period if administered for sclerotic-type chronic graft versus host disease (ScGVHD). Response is joint ROM: increase of >25% in composite ROM score. Maximal response is a response with no further improvement over 2 sequential 3-month evaluations. Stable disease does not meet the criteria for progression, response, or maximal response.
6 secondary outcomes
Number of Participants With Adverse Events
Time frame: Date treatment consent signed to date off study, approximately, 41 months, 27 days
Average Percentage Change in Range of Motion (ROM) Deficit
Time frame: 6 months
Total Skin Score at Baseline and 6 Months
Time frame: Baseline and 6 Months
Total Chronic Graft Versus Host Disease (cGVHD) Provider Global Rating Score at Baseline and 6 Months
Time frame: Baseline and 6 months
Lung Function Score at Baseline and 6 Months
Time frame: Baseline and 6 Months
Change in Immunosuppression
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25771402Baird K, Comis LE, Joe GO, Steinberg SM, Hakim FT, Rose JJ, Mitchell SA, Pavletic SZ, Figg WD, Yao L, Flanders KC, Takebe N, Sarantopoulos S, Booher S, Cowen EW. Imatinib mesylate for the treatment of steroid-refractory sclerotic-type cutaneous chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2015 Jun;21(6):1083-90. doi: 10.1016/j.bbmt.2015.03.006. Epub 2015 Mar 12.
- Derived from this study: PubMed 31811481Rosenthal EA, Ho PS, Joe GO, Mitchell SA, Booher S, Pavletic SZ, Baird K, Cowen EW, Comis LE. Motor ability, function, and health-related quality of life as correlates of symptom burden in patients with sclerotic chronic graft-versus-host disease receiving imatinib mesylate. Support Care Cancer. 2020 Aug;28(8):3679-3689. doi: 10.1007/s00520-019-05207-z. Epub 2019 Dec 6.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward W Cowen, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gleevec, STI571(Imatinib Mesylate) in people with Sclerotic Graft Versus Host Disease and Imatinib Mesylate, run by National Cancer Institute (NCI) at 1 site 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 26 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 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 19 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT00702689, which also lists 2 linked publications.
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 30 Mar 2020.