Graft Versus Host DiseasePhase 3NCT00562497
Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute Graft Versus Host Disease (GVHD)
A Phase 3 study testing Prochymal® and Corticosteroid in people with Graft Versus Host Disease, run by Mesoblast, Inc. at 53 sites in 3 countries.
Trial summary
This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Prochymal® and Corticosteroid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 53 sitesin 3 countries
- Study dates
- 31 Jan 2008to 20 May 2010
- Phase
- Phase 3
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be 18 years to 70 years of age, inclusive
- Participants must have received an allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood or administered a donor leukocyte infusion.
- Participants must have newly diagnosed Grades B-D acute GVHD. Biopsy confirmation of GVHD is strongly recommended but not required. Randomization should not be delayed awaiting biopsy or pathology results.
- Participants must be randomized and treated with corticosteroid (1-2 mg/kg/d methylprednisolone, or equivalent) and Prochymal®/placebo within 72 hours of onset of acute GVHD.
- Participants must have adequate renal function as defined by: Calculated Creatinine Clearance of >30 mL/min using the Cockcroft-Gault equation
- Participants who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male participants must use adequate contraception
- Participant must have a minimum Karnofsky Performance Level of at least 30 at the time of study entry
- Participant (or legal representative where appropriate) must be capable of providing written informed consent.
Who cannot join
- Participant has been previously treated with systemic immunosuppressive therapy for acute GVHD
- Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant including uncontrolled infection, heart failure, pulmonary hypertension, etc.
- Participants may not receive any other investigational agents (not approved by the FDA for any indication) concurrently during study participation or within 30 days of randomization.
- Participant has a known allergy to bovine or porcine products or dimethyl sulfoxide (DMSO)
- Participant has received a transplant for a solid tumor disease.
- Participant requires more than 2 liters/min of oxygen to maintain stable oxygen saturation (Sa02) greater than or equal to 92%
- Participant requires a renal dopamine dose greater than 1-3 mcg/kg/min to maintain renal blood flow associated with renal failure and improved urinary output.
Trial locations and contacts
53 sites in 3 countries.
53 sites in 3 countries
United States45 sites
Emory University
Atlanta, Georgia, 30322
Northside Hospital
Atlanta, Georgia, 30342
University of Alabama Birmingham (UAB) Hospital
Birmingham, Alabama, 35249
Tufts New England Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27514
Medical University of South Carolina(MUSC)
Charleston, South Carolina, 29425
Northwestern Center for Clinical Research
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Chicago Hospitals
Chicago, Illinois, 60637
Jewish Hospital
Cincinnati, Ohio, 45236
Ohio State University
Columbus, Ohio, 43210
Baylor University Medical Center
Dallas, Texas, 75246
Rocky Mountain Cancer Center
Denver, Colorado, 80218
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University Health System
Durham, North Carolina, 27705
University of Florida
Gainesville, Florida, 32610
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Cancer Center
Indianapolis, Indiana, 46202
St. Francis Cancer Center
Indianapolis, Indiana, 46237
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Kansas City Cancer Center
Lee's Summit, Missouri, 64064
UCLA Medical Center
Los Angeles, California, 90095
University of Louisville
Louisville, Kentucky, 40202
Loyola University Medical Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Mount Sinai School of Medicine
New York, New York, 10029
New York Presbyterian Hospital
New York, New York, 10065
Abramson Cancer Center, University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224
Oncology Hematology Association
Pittsburgh, Pennsylvania, 15232
University of Pittsburgh Cancer Centers
Pittsburgh, Pennsylvania, 15232
Virginia Commonwealth University
Richmond, Virginia, 23298
Mayo Medical Center
Rochester, Minnesota, 55905
Texas Transplant Institute
San Antonio, Texas, 78229
University of California Medical Center
San Francisco, California, 94143
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
Australia5 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
St. Vincent's Hospital
Darlinghurst, NSW 2010
Royal Brisbane Hospital
Herston, QLD 4029
Royal Melbourne Hospital
Parkville, Victoria, 3050
Royal Perth Hospital
Perth, Western Australia, 6001
Canada3 sites
Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD
This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients with previously untreated acute GVHD and the historical published data define an expected 35% complete response (CR) at Day +28 using this therapy.
Read the detailed description
Participants will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. The first infusion of the investigational product (IP) will be administered within 72 hours of the start of systemic corticosteroid therapy. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Participants assigned to the active treatment group will receive Prochymal®. Participants assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all participants receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.
Participants will be evaluated for efficacy and safety until death, withdrawal or 90 study days after randomization, whichever occurs first. Study will be unblinded and data analyzed at Day 90 post 1st infusion (Day 0) following final participant enrollment. Participants will be followed for safety for 12 months post 1st infusion (Day 0).
- Conditions
- Graft Versus Host Disease
- Being tested
- Prochymal®, Placebo, Corticosteroid
- Keywords
- Acute GVHD, Acute 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.
Prochymal®Drug
Also called Remestemcel-L
Prochymal® intravenous infusion.
PlaceboOther
Placebo-matching Prochymal® intravenous infusion.
CorticosteroidOther
Also called Methylprednisolone, Prednisone
Administration will be intravenously as prescribed by the caregiver.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive 6 infusions of placebo-matching Prochymal® intravenously (IV) during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. Receives: Other: Placebo; Other: Corticosteroid |
| Prochymal® 2x10^6 hMSC/kg | Active comparator | Participants will receive 6 infusions of Prochymal® 2x10^6 human mesenchymal stem cells (hMSC)/kg IV during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. Receives: Drug: Prochymal®; Other: Corticosteroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants with Treatment Success
Treatment was considered a success if all of the following conditions were met: Achieved induction of a complete response (CR) within 28 days after first infusion; CR followed by 28 days maintenance of a clinically meaningful response defined as the response that did not require an increase in corticosteroid dose (methylprednisolone doses >2 milligram/kilogram/day [mg/kg/d] or prednisone doses >2.5 mg/kg/d) for more than 7 consecutive days; Did not require second line/escalation therapy through Study Day 56; and survived 90 study days.
Measured: 90 Days
Secondary outcomes (12)
Percentage of Participants with Overall Response
Overall Response was defined as participants who achieved complete response or partial response (CR+PR).
Measured: Day 90
Percentage of Participants with Induction of a 2-grade decrease in (Graft Versus Host Disease) GVHD by Study Day 28 with maintenance of a 2-grade decrease in GVHD through Study Day 56
Measured: Up to Day 56
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
Measured: Day 14
Percentage of Participants with Induction of a CR after Study Day 28 and clinically managed with steroids with second line/escalation therapy through Study Day 56
Measured: Up to Day 56
Percentage of Participants with Induction of PR during the first 28 days
Measured: Up to Day 28
Time to achieve CR
Measured: Up to Day 90
Number of CR per organ
Measured: Up to Day 90
Total corticosteroid dose administered
Measured: Up to Day 90
Number of corticosteroid-related complications
Corticosteroid-related complications included hyperglycemia requiring insulin, corticosteroid myopathy and psychosis.
Measured: Up to Day 90
Number of Infectious complications
Infectious complications included viral, fungal or bacterial complications.
Measured: Up to Day 90
Number of Days of Hospitalization
Measured: Up to Day 90
Average Daily Corticosteroid Dose
Measured: Up to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2007 (estimated)
- Study start31 Jan 2008
- Primary completion14 Jul 2009
- Study completion20 May 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mesoblast, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christopher James, PA, Study director, Mesoblast, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00562497
- Sponsor's protocol ID
- 265
- Status last verified
- Jan 2022
- First submitted
- 20 Nov 2007
- Last updated
- 19 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD
- ClinicalTrials.gov ID
- NCT00562497
- Acronym / sponsor ID
- 265
- Conditions
- Graft Versus Host Disease
- Keywords
- Acute GVHD, Acute Graft Versus Host Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Mesoblast, Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Jan 2008 (actual)
- Primary completion
- 14 Jul 2009 (actual)
- Study completion
- 20 May 2010 (actual)
- First posted
- 22 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal® versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients with previously untreated acute GVHD and the historical published data define an expected 35% complete response (CR) at Day +28 using this therapy.
Detailed description
Participants will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. The first infusion of the investigational product (IP) will be administered within 72 hours of the start of systemic corticosteroid therapy. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Participants assigned to the active treatment group will receive Prochymal®. Participants assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all participants receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.
Participants will be evaluated for efficacy and safety until death, withdrawal or 90 study days after randomization, whichever occurs first. Study will be unblinded and data analyzed at Day 90 post 1st infusion (Day 0) following final participant enrollment. Participants will be followed for safety for 12 months post 1st infusion (Day 0).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo, Other: CorticosteroidParticipants will receive 6 infusions of placebo-matching Prochymal® intravenously (IV) during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. |
| Prochymal® 2x10^6 hMSC/kg | Active comparator | Drug: Prochymal®, Other: CorticosteroidParticipants will receive 6 infusions of Prochymal® 2x10^6 human mesenchymal stem cells (hMSC)/kg IV during the first 4 weeks of the study. The first infusion will be administered within 72 hours of the start of systemic corticosteroid therapy. Participants will receive 4 infusions during the first 2 weeks (twice weekly at least 3 days apart), followed by 2 infusions administered once weekly over the subsequent 2 weeks up to Day 28. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Participants must be 18 years to 70 years of age, inclusive
- Participants must have received an allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood or administered a donor leukocyte infusion.
- Participants must have newly diagnosed Grades B-D acute GVHD. Biopsy confirmation of GVHD is strongly recommended but not required. Randomization should not be delayed awaiting biopsy or pathology results.
- Participants must be randomized and treated with corticosteroid (1-2 mg/kg/d methylprednisolone, or equivalent) and Prochymal®/placebo within 72 hours of onset of acute GVHD.
- Participants must have adequate renal function as defined by: Calculated Creatinine Clearance of >30 mL/min using the Cockcroft-Gault equation
Key exclusion criteria (7 listed)
- Participant has been previously treated with systemic immunosuppressive therapy for acute GVHD
- Participant has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant including uncontrolled infection, heart failure, pulmonary hypertension, etc.
- Participants may not receive any other investigational agents (not approved by the FDA for any indication) concurrently during study participation or within 30 days of randomization.
- Participant has a known allergy to bovine or porcine products or dimethyl sulfoxide (DMSO)
- Participant has received a transplant for a solid tumor disease.
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 |
|---|---|---|
| Prochymal®Also: Remestemcel-LProchymal® intravenous infusion. | Drug | Prochymal® 2x10^6 hMSC/kg |
| PlaceboPlacebo-matching Prochymal® intravenous infusion. | Other | Placebo |
| CorticosteroidAlso: Methylprednisolone, PrednisoneAdministration will be intravenously as prescribed by the caregiver. | Other | Placebo, Prochymal® 2x10^6 hMSC/kg |
Primary outcome
Percentage of Participants with Treatment Success
Time frame: 90 Days
Treatment was considered a success if all of the following conditions were met: Achieved induction of a complete response (CR) within 28 days after first infusion; CR followed by 28 days maintenance of a clinically meaningful response defined as the response that did not require an increase in corticosteroid dose (methylprednisolone doses >2 milligram/kilogram/day [mg/kg/d] or prednisone doses >2.5 mg/kg/d) for more than 7 consecutive days; Did not require second line/escalation therapy through Study Day 56; and survived 90 study days.
12 secondary outcomes
Percentage of Participants with Overall Response
Time frame: Day 90
Percentage of Participants with Induction of a 2-grade decrease in (Graft Versus Host Disease) GVHD by Study Day 28 with maintenance of a 2-grade decrease in GVHD through Study Day 56
Time frame: Up to Day 56
Percentage of Participants with Induction of CR lasting for greater than or equal to 14 Days
Time frame: Day 14
Percentage of Participants with Induction of a CR after Study Day 28 and clinically managed with steroids with second line/escalation therapy through Study Day 56
Time frame: Up to Day 56
Percentage of Participants with Induction of PR during the first 28 days
Time frame: Up to Day 28
Time to achieve CR
Time frame: Up to Day 90
Number of CR per organ
Time frame: Up to Day 90
Total corticosteroid dose administered
Time frame: Up to Day 90
Number of corticosteroid-related complications
Time frame: Up to Day 90
Number of Infectious complications
Time frame: Up to Day 90
Number of Days of Hospitalization
Time frame: Up to Day 90
Average Daily Corticosteroid Dose
Time frame: Up to Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2022.
- Click here for more information about this study: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal® Infusion in Combination With Corticosteroids for the Treatment of Newly DiagnosedLink provided by the sponsor.
Related trials for Graft Versus Host Disease
Active, not recruitingPhase 2
De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis
Graft-versus-host Disease
RecruitingEarly Phase 1
HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Hematologic Malignancy
RecruitingObservational study
Improved Methods of Cell Selection for Bone Marrow Transplant Alternatives
Graft-Versus-Host Disease, Graft-versus-leukemia
RecruitingPhase 1/2
The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantation
Peripheral Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
RecruitingPhase 1/2
Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Graft vs Host Disease
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.
Christopher James, PA study director
Mesoblast, Inc.
53 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Prochymal® and Corticosteroid in people with Graft Versus Host Disease, run by Mesoblast, Inc. at 53 sites in 3 countries.
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 7 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 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Australia, Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Percentage of Participants with Treatment Success (time frame: 90 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jan 2022.