Graft Vs Host DiseasePhase 2NCT00136903
Safety and Efficacy Study of Adult Human Mesenchymal Stem Cells to Treat Acute Graft Versus Host Disease (GVHD)
A Phase 2 study testing Prochymal® - 2 Million cells/kg, Prochymal®- 8 Million cells/kg and Methylprednisolone in people with Graft Vs Host Disease, run by Mesoblast, Inc. at 9 sites in United States.
Trial summary
To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Graft Vs Host Disease
- What is being tested?
- Prochymal® - 2 Million cells/kg, Prochymal®- 8 Million cells/kg and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 9 sitesUnited States
- Study dates
- 27 Apr 2005to 14 Jul 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Protocol 260 Inclusion Criteria:
- Participant must be 18 to 70 years of age inclusive.
- If female and of child-bearing age, participant must be non-pregnant, not breast feeding, and use adequate contraception. Males must use adequate contraception.
- Participant must have newly diagnosed, Grade II-IV acute GVHD requiring therapy. Biopsy for confirmation of GVHD is not mandatory, but is recommended when feasible. Enrollment should not be delayed awaiting biopsy results.
- Participant must have received either full or reduced intensity myeloablative regimens followed by an allogeneic hematopoietic stem cell transplant using bone marrow, peripheral blood stem cell, or cord blood, including donor lymphocyte infusion (DLI).
- Participant must have minimal renal and hepatic function as defined by:
- Calculated creatinine clearance (CLcr) of > 30 mL/min using the Cockroft-Gault equation.
- Participant must be available for all specified assessments at the study site through study Day 28.
- Participant must provide written informed consent and authorization for use and disclosure of protected health information (PHI).
Protocol 260 Exclusion Criteria:
- Participant has received previous treatment for Grade II-IV acute GVHD (except as noted in Criterion 2).
- Participant has been treated for GVHD with methylprednisolone, > 2mg/kg/day, for more than 72 hours prior to receiving Prochymal®.
- Participant has uncontrolled alcohol or substance abuse within 6 months of randomization.
- Participant has received an investigational agent (not approved by food and drug administration (FDA) for marketed use in any indication) within 30 days of randomization. Participant may not receive an investigational agent during the 28-day study period.
- 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 (e.g., uncontrolled infection, right heart failure, pulmonary hypertension, etc.).
- Participant has unstable arrhythmia.
- Participant is unwilling to sign consent form for the long-term follow-up study, Protocol 261.
- Participant has a known allergy to bovine or porcine products.
- Participant had received transplant for a solid tumor disease.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
The Cancer Center at Hackensack University
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
St. Francis Hospital
Indianapolis, Indiana, 46237
Kansas City Cancer Centers - BMT
Kansas City, Missouri, 64111
Medical College of Wisconsin, FEC
Milwaukee, Wisconsin, 53226
Mt. Sinai Hospital
New York, New York, 10029
University of Rochester
Rochester, New York, 14642
New York Medical College
Valhalla, New York, 10595
About this study
Official title: A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) For the Treatment of Acute GVHD in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation
To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant.
Read the detailed description
Protocol 260 - Participants will be randomized with equal probability to the treatment arms (2 million cells/kilogram (kg) of Prochymal® or 8 million cells/kg of Prochymal®) using a stratified block design. The stratification factor is acute GVHD grade. For the purpose of stratification, the GVHD grades are II and III-IV. Treatment with investigational agent will be administered on study Days 1 and 4. Participants will be followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurs first.
Protocol 261- This study is designed as a long-term safety follow-up of participants who take part in the preceding clinical study of Prochymal® (Protocol 260) for the treatment of acute GVHD. Participants will be enrolled in Study 261 upon completion of the preceding Study 260.
- Conditions
- Graft Vs Host Disease
- Being tested
- Prochymal® - 2 Million cells/kg, Prochymal®- 8 Million cells/kg, Methylprednisolone, Prednisone, Cyclosporine
- Keywords
- Graft vs Host Disease, (GVHD), Graft Versus Host Disease, Bone marrow transplant, Stem cells, Mesenchymal stem cells (MSCs), Adult stem cells, Leukemia, Lymphoma
- Medical subject headings
- Graft vs Host Disease, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prochymal® - 2 Million cells/kgDrug
Also called Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs
2 million hMSCs/kg actual body weight, IV on study Days 1 and 4
Prochymal®- 8 Million cells/kgDrug
Also called Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs
8 million hMSCs/kg actual body weight IV on study Days 1 and 4
Methylprednisolone 2 mg/kg administered intravenously.
PrednisoneDrug
Prednisone 2.5 mg/kg administered orally.
CyclosporineDrug
Administered as prescribed by the caregiver.
TacrolimusDrug
Administered as prescribed by the caregiver.
Administered as prescribed by the caregiver.
| Study group | Role | What they receive |
|---|---|---|
| Prochymal® - 2 Million cells/kg | Active comparator | Participants will receive Prochymal® consisting of 2 million hMSCs/kg actual body weight, intravenously (IV) on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 milligrams (mg)/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. Receives: Drug: Prochymal® - 2 Million cells/kg; Drug: Methylprednisolone; Drug: Prednisone; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil |
| Prochymal® - 8 Million cells/kg | Active comparator | Participants will receive Prochymal® consisting of 8 million hMSCs/kg actual body weight IV on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 mg/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. Receives: Drug: Prochymal®- 8 Million cells/kg; Drug: Methylprednisolone; Drug: Prednisone; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)
Measured: 28 Days
Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).
Measured: 2 Years
Secondary outcomes (4)
Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1,
Measured: 28 Days
Protocol 260 - Time to best response of GVHD
Measured: 28 Days
Protocol 260 - Time to improvement of GVHD in one or more organs
Measured: 28 Days
Protocol 261 - Survival through study day 90
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2005 (estimated)
- Study start27 Apr 2005
- Primary completion28 Jul 2006
- Study completion14 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Graft Vs 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT00136903
- Sponsor's protocol ID
- 260-261
- Status last verified
- Jan 2022
- First submitted
- 25 Aug 2005
- Last updated
- 31 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002 Jan;30(1):42-8. doi: 10.1016/s0301-472x(01)00769-x.
PubMed 11823036Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. doi: 10.1016/s0301-472x(00)00482-3.
PubMed 10989188Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005 May;11(5):389-98. doi: 10.1016/j.bbmt.2005.02.001.
PubMed 15846293Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.
PubMed 15121408Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.
PubMed 16040382Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M, Monroy R, Uberti J. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009 Jul;15(7):804-11. doi: 10.1016/j.bbmt.2008.03.012.
PubMed 19539211
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Prochymal® (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) For the Treatment of Acute GVHD in Patients Who Receive Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00136903
- Acronym / sponsor ID
- 260-261
- Conditions
- Graft Vs Host Disease
- Keywords
- Graft vs Host Disease, (GVHD), Graft Versus Host Disease, Bone marrow transplant, Stem cells, Mesenchymal stem cells (MSCs), Adult stem cells, Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Mesoblast, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Apr 2005 (actual)
- Primary completion
- 28 Jul 2006 (actual)
- Study completion
- 14 Jul 2008 (actual)
- First posted
- 29 Aug 2005 (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.
To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant.
Detailed description
Protocol 260 - Participants will be randomized with equal probability to the treatment arms (2 million cells/kilogram (kg) of Prochymal® or 8 million cells/kg of Prochymal®) using a stratified block design. The stratification factor is acute GVHD grade. For the purpose of stratification, the GVHD grades are II and III-IV. Treatment with investigational agent will be administered on study Days 1 and 4. Participants will be followed for safety and efficacy until Day 28 after initiation of treatment with the investigational agent, or until withdrawal or death, whichever occurs first.
Protocol 261- This study is designed as a long-term safety follow-up of participants who take part in the preceding clinical study of Prochymal® (Protocol 260) for the treatment of acute GVHD. Participants will be enrolled in Study 261 upon completion of the preceding Study 260.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prochymal® - 2 Million cells/kg | Active comparator | Drug: Prochymal® - 2 Million cells/kg, Drug: Methylprednisolone, Drug: Prednisone, Drug: Cyclosporine, Drug: Tacrolimus, Drug: Mycophenolate MofetilParticipants will receive Prochymal® consisting of 2 million hMSCs/kg actual body weight, intravenously (IV) on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 milligrams (mg)/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. |
| Prochymal® - 8 Million cells/kg | Active comparator | Drug: Prochymal®- 8 Million cells/kg, Drug: Methylprednisolone, Drug: Prednisone, Drug: Cyclosporine, Drug: Tacrolimus, Drug: Mycophenolate MofetilParticipants will receive Prochymal® consisting of 8 million hMSCs/kg actual body weight IV on Days 1 and 4 along with daily standard of care which includes methylprednisolone 2 mg/kg IV or prednisone 2.5 mg/kg orally. Participants will also continue cyclosporine, tacrolimus, and/or mycophenolate mofetil (MMF) at full therapeutic doses. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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® - 2 Million cells/kgAlso: Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs2 million hMSCs/kg actual body weight, IV on study Days 1 and 4 | Drug | Prochymal® - 2 Million cells/kg |
| Prochymal®- 8 Million cells/kgAlso: Remestemcel-L, ex-vivo cultured adult human mesenchymal stem cells, hMSCs8 million hMSCs/kg actual body weight IV on study Days 1 and 4 | Drug | Prochymal® - 8 Million cells/kg |
| MethylprednisoloneMethylprednisolone 2 mg/kg administered intravenously. | Drug | Prochymal® - 2 Million cells/kg, Prochymal® - 8 Million cells/kg |
| PrednisonePrednisone 2.5 mg/kg administered orally. | Drug | Prochymal® - 2 Million cells/kg, Prochymal® - 8 Million cells/kg |
| CyclosporineAdministered as prescribed by the caregiver. | Drug | Prochymal® - 2 Million cells/kg, Prochymal® - 8 Million cells/kg |
| TacrolimusAdministered as prescribed by the caregiver. | Drug | Prochymal® - 2 Million cells/kg, Prochymal® - 8 Million cells/kg |
| Mycophenolate MofetilAdministered as prescribed by the caregiver. | Drug | Prochymal® - 2 Million cells/kg, Prochymal® - 8 Million cells/kg |
Primary outcome
Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)
Time frame: 28 Days
Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).
Time frame: 2 Years
4 secondary outcomes
Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1,
Time frame: 28 Days
Protocol 260 - Time to best response of GVHD
Time frame: 28 Days
Protocol 260 - Time to improvement of GVHD in one or more organs
Time frame: 28 Days
Protocol 261 - Survival through study day 90
Time frame: 90 Days
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 31 Jan 2022.
- Background: PubMed 11823036Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002 Jan;30(1):42-8. doi: 10.1016/s0301-472x(01)00769-x.
- Background: PubMed 10989188Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. doi: 10.1016/s0301-472x(00)00482-3.
- Background: PubMed 15846293Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005 May;11(5):389-98. doi: 10.1016/j.bbmt.2005.02.001.
- Background: PubMed 15121408Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.
- Background: PubMed 16040382Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.
- Results publication: PubMed 19539211Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M, Monroy R, Uberti J. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009 Jul;15(7):804-11. doi: 10.1016/j.bbmt.2008.03.012.
- Click here for more information on Prochymal® for treatment of GVHDLink provided by the sponsor.
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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.
9 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 Prochymal® - 2 Million cells/kg, Prochymal®- 8 Million cells/kg and Methylprednisolone in people with Graft Vs Host Disease, run by Mesoblast, Inc. at 9 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?
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 31 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 9 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?
Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR) (time frame: 28 Days). 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 NCT00136903, which also lists 6 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 31 Jan 2022.