Graft Versus Host DiseasePhase 2NCT01309997
Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease
A Phase 2 study testing imatinib mesylate and rituximab in people with Graft Versus Host Disease and Systemic Scleroderma, run by Lee, Stephanie at 10 sites in United States.
Trial summary
This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Graft Versus Host Disease, Systemic Scleroderma
- What is being tested?
- imatinib mesylate and rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 10 sitesUnited States
- Study dates
- Mar 2011to Dec 2015
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis within the past 18 months of cutaneous sclerosis after hematopoietic cell transplant (HCT) with sclerotic skin, morphea, myofascial involvement or joint contractures; must have a score of 2 or greater on the Vienna skin scale in any area, or a range-of-motion (ROM) score of 5 or less at the shoulder, elbow or wrist, or 3 or less at the ankle
- No medication added for the treatment of graft versus host disease (GVHD) within the past 4 weeks
- Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated
- Age 2-99 years
- Karnofsky performance status >= 60% at enrollment
- All females of childbearing potential must have a negative serum or urine pregnancy test =< 7 days prior to starting study therapy
- All females of childbearing potential must agree to use a form of Food and Drug Administration (FDA) approved contraception from enrollment to one month after study treatment ends
- Subject has the ability to understand and willingness to sign a written informed consent document
Who cannot join
- Total bilirubin > 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Renal insufficiency (serum creatinine > 2.0 mg/dl)
- Platelets < 30,000/ul or absolute neutrophil count < 1500/ul
- Known hypersensitivity to rituximab or other anti-B cell antibodies
- Known imatinib intolerance or allergy
Show all 22Show fewer
- Evidence of any active viral, bacterial, or fungal infection that is progressive despite appropriate treatment
- Hepatitis B surface antigen positive
- Hepatitis B core antibody positive, unless hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable
- Hepatitis C antibody positive, unless hepatitis C virus (HCV) ribonucleic acid (RNA) is undetectable
- Pregnant, lactating, or planning a pregnancy while in the study
- Distal leg skin score 3 or higher as the only manifestation of sclerosis
- Prior treatment of chronic GVHD with imatinib, rituximab, or any other monoclonal B-cell antibody (e.g. ofatumumab)
- Receipt of imatinib within the previous 6 months for any indication
- Receipt of any monoclonal B-cell antibody (e.g. rituximab, ofatumumab) within the previous 12 months for any indication
- Treatment with anti-B-cell cellular therapy (e.g. chimeric antigen-receptor-engineered cells) at any time after transplant
- Current treatment with extracorporeal photopheresis (ECP) at the time of enrollment
- History of psychiatric disorder that would interfere with normal participation in this study
- Inability or unwillingness of subject and/or parent guardian to provide informed consent or comply with study protocol
- Use of non-FDA approved drugs within 4 weeks of participation
- Patient with any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements
- Patients with uncontrolled substance abuse
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina
Chapel Hill, North Carolina, 27599
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Weill Cornell Medical College
New York, New York, 10065
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Hospitals and Clinics
Stanford, California, 94305
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the best clinical response rate of cutaneous sclerosis (skin and/or fascial thickening) after 6 months of initial therapy with either imatinib (imatinib mesylate) or rituximab.
SECONDARY OBJECTIVES:
- To determine the best response at either the 3 or 6 month assessment.
II. To determine the response rate at the 3 month assessment.
III. To determine the proportion of subjects who are able to taper corticosteroid after 6 months of imatinib or rituximab therapy.
IV. To determine the incidence of treatment failure to initial treatment with either imatinib or rituximab.
- To evaluate if the Scleroderma Health Assessment Questionnaire (SHAQ) findings correlate with severity of cutaneous sclerosis clinical findings and response to study treatment.
VI. To correlate the detection of antibody against platelet derived growth factor receptor alpha (PDGFR A) with clinical response.
VII. To correlate change in B cell relevant parameters from baseline to 6 months or early crossover (antibody levels, skin collagen expression, B cell subsets) with therapeutic agent and best clinical response while on initial treatment.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive imatinib mesylate by mouth (PO) once daily (QD) for 6 months in the absence of progression of sclerosis or unacceptable toxicity. Subjects with a significant clinical response will continue to receive study drug for an additional 6 months.
ARM II: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22 (first cycle). A second cycle of treatment with rituximab is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity.
Patients with progression, treatment intolerance at any time up to 6 months, or no clinical response at 6 months will crossover to the other treatment arm.
- Conditions
- Graft Versus Host Disease, Systemic Scleroderma
- Being tested
- imatinib mesylate, rituximab
- Keywords
- Imatinib, Rituximab, Chronic Graft-vs-Host Disease
- Medical subject headings
- Graft vs Host Disease, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
Also called CGP 57148, Gleevec, Glivec
Given PO
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (enzyme inhibitor) | Experimental | Patients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity. Receives: Drug: imatinib mesylate |
| Arm II (monoclonal antibody) | Experimental | Patients receive rituximab IV on days 1, 8, 15, and 22. A second treatment cycle is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity. Receives: Biological: rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Significant Clinical Response
Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 [worst] to 2, 3 to 1, or 2 to 0 [best]) without a concurrent increase of two or more points in another area OR by an increase in the range of motion of the shoulders, elbows or wrists by two points (in a 1-7 scale where 1 is worst and 7 is best) or of the ankles by one point (in a 1 to 4 scale where 1 is worst and 4 is best) without a concurrent worsening in another area.
Measured: 6 months
Secondary outcomes (6)
Patients Who Were Able to Taper Corticosteroids
Patients who achieved a greater than or equal to 50% reduction in the daily corticosteroid dose at 6mo compared to baseline
Measured: 6 months
Cumulative Incidence of Treatment Failure
Defined as discontinuation of randomized treatment due to chronic GVHD progression or treatment intolerance or no significant clinical response in sclerosis.
Measured: 6 months
Number of Patients Achieving Improvement in Cutaneous Sclerosis
Assessed by decrease of >= 0.2 units (where 0 is best and 3.0 is worst ) in the Scleroderma Health Assessment Questionnaire (SHAQ).
Measured: 6 months
Baseline Histopathologic Score in the Two Treatment Arms
Instrument: Nash dermal fibrosis grade. Measures extent of sclerosis in skin biopsies by histologic examination. Scale ranges from grade 0-5. Nash grade 5 is most severe fibrosis (0 is better outcome, 5 is worse outcome). No subscales are used in Nash grade. Please see table 1 in the reference for grading of dermal fibrosis.
Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007;110:1388-96.
Measured: Enrollment
Patients With Any Percentage Decline in Any Grade of Sclerosis Without Increase in Percentage of Higher Grades of Sclerosis in Other Areas on the Vienna Skin Scale
Maximum of 10 body areas. Each area can be graded 0 (best) to 4 (worst). Each of those grades requires a percentage of involvement. Improvement is measured by reduction of involvement in any grade and any body area.
Measured: 6 months
Percentage of CD27+ B Cells in Responders (SCR) and Non-responders
%CD27+ B cells
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 posted7 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2014
- Study completionDec 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lee, Stephanie
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Lee, Stephanie, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
- Investigators
- Stephanie Lee, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01309997
- Sponsor's protocol ID
- 2343.00
- Other IDs
- NCI-2011-00098, RDCRN 6502, 2343.00, U54CA163438, P30CA015704
- Status last verified
- May 2016
- First submitted
- 1 Mar 2011
- Last updated
- 15 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified patient data and samples may be available with the appropriate approvals. Contact the PI for information.
Publications
Arai S, Pidala J, Pusic I, Chai X, Jaglowski S, Khera N, Palmer J, Chen GL, Jagasia MH, Mayer SA, Wood WA, Green M, Hyun TS, Inamoto Y, Storer BE, Miklos DB, Shulman HM, Martin PJ, Sarantopoulos S, Lee SJ, Flowers ME. A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clin Cancer Res. 2016 Jan 15;22(2):319-27. doi: 10.1158/1078-0432.CCR-15-1443. Epub 2015 Sep 16.
PubMed 26378033
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT01309997
- Acronym / sponsor ID
- 2343.00
- Conditions
- Graft Versus Host Disease, Systemic Scleroderma
- Keywords
- Imatinib, Rituximab, Chronic Graft-vs-Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Lee, StephanieUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 7 Mar 2011 (estimated)
- Results
- Posted 15 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.
Detailed description
PRIMARY OBJECTIVES:
- To determine the best clinical response rate of cutaneous sclerosis (skin and/or fascial thickening) after 6 months of initial therapy with either imatinib (imatinib mesylate) or rituximab.
SECONDARY OBJECTIVES:
- To determine the best response at either the 3 or 6 month assessment.
II. To determine the response rate at the 3 month assessment.
III. To determine the proportion of subjects who are able to taper corticosteroid after 6 months of imatinib or rituximab therapy.
IV. To determine the incidence of treatment failure to initial treatment with either imatinib or rituximab.
- To evaluate if the Scleroderma Health Assessment Questionnaire (SHAQ) findings correlate with severity of cutaneous sclerosis clinical findings and response to study treatment.
VI. To correlate the detection of antibody against platelet derived growth factor receptor alpha (PDGFR A) with clinical response.
VII. To correlate change in B cell relevant parameters from baseline to 6 months or early crossover (antibody levels, skin collagen expression, B cell subsets) with therapeutic agent and best clinical response while on initial treatment.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive imatinib mesylate by mouth (PO) once daily (QD) for 6 months in the absence of progression of sclerosis or unacceptable toxicity. Subjects with a significant clinical response will continue to receive study drug for an additional 6 months.
ARM II: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22 (first cycle). A second cycle of treatment with rituximab is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity.
Patients with progression, treatment intolerance at any time up to 6 months, or no clinical response at 6 months will crossover to the other treatment arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (enzyme inhibitor) | Experimental | Drug: imatinib mesylatePatients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity. |
| Arm II (monoclonal antibody) | Experimental | Biological: rituximabPatients receive rituximab IV on days 1, 8, 15, and 22. A second treatment cycle is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis within the past 18 months of cutaneous sclerosis after hematopoietic cell transplant (HCT) with sclerotic skin, morphea, myofascial involvement or joint contractures; must have a score of 2 or greater on the Vienna skin scale in any area, or a range-of-motion (ROM) score of 5 or less at the shoulder, elbow or wrist, or 3 or less at the ankle
- No medication added for the treatment of graft versus host disease (GVHD) within the past 4 weeks
- Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated
- Age 2-99 years
- Karnofsky performance status >= 60% at enrollment
Key exclusion criteria (22 listed)
- Total bilirubin > 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Renal insufficiency (serum creatinine > 2.0 mg/dl)
- Platelets < 30,000/ul or absolute neutrophil count < 1500/ul
- Known hypersensitivity to rituximab or other anti-B cell antibodies
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 |
|---|---|---|
| imatinib mesylateAlso: CGP 57148, Gleevec, GlivecGiven PO | Drug | Arm I (enzyme inhibitor) |
| rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV | Biological | Arm II (monoclonal antibody) |
Primary outcome
Significant Clinical Response
Time frame: 6 months
Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 [worst] to 2, 3 to 1, or 2 to 0 [best]) without a concurrent increase of two or more points in another area OR by an increase in the range of motion of the shoulders, elbows or wrists by two points (in a 1-7 scale where 1 is worst and 7 is best) or of the ankles by one point (in a 1 to 4 scale where 1 is worst and 4 is best) without a concurrent worsening in another area.
6 secondary outcomes
Patients Who Were Able to Taper Corticosteroids
Time frame: 6 months
Cumulative Incidence of Treatment Failure
Time frame: 6 months
Number of Patients Achieving Improvement in Cutaneous Sclerosis
Time frame: 6 months
Baseline Histopathologic Score in the Two Treatment Arms
Time frame: Enrollment
Patients With Any Percentage Decline in Any Grade of Sclerosis Without Increase in Percentage of Higher Grades of Sclerosis in Other Areas on the Vienna Skin Scale
Time frame: 6 months
Percentage of CD27+ B Cells in Responders (SCR) and Non-responders
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 15 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26378033Arai S, Pidala J, Pusic I, Chai X, Jaglowski S, Khera N, Palmer J, Chen GL, Jagasia MH, Mayer SA, Wood WA, Green M, Hyun TS, Inamoto Y, Storer BE, Miklos DB, Shulman HM, Martin PJ, Sarantopoulos S, Lee SJ, Flowers ME. A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clin Cancer Res. 2016 Jan 15;22(2):319-27. doi: 10.1158/1078-0432.CCR-15-1443. Epub 2015 Sep 16.
- Individual participant dataSharing planned: Yes. De-identified patient data and samples may be available with the appropriate approvals. Contact the PI for information.
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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.
Stephanie Lee principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imatinib mesylate and rituximab in people with Graft Versus Host Disease and Systemic Scleroderma, run by Lee, Stephanie at 10 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 8 inclusion and 22 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 15 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
Yes. Results are posted in the registry (first posted 15 Jun 2016). 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?
Significant Clinical Response (time frame: 6 months). 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 NCT01309997, 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 15 Jun 2016.