Grade B aGVHDPhase 3NCT02336230

A Prospective Study of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Participants Who Have Failed to Respond to Steroid Treatment for Acute Graft-Versus-Host Disease (aGVHD)

A Phase 3 study testing remestemcel-L in people with Grade B aGVHD and Grade C aGVHD, run by Mesoblast, Inc. at 20 sites in United States.

Completed

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

Official record

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Trial summary

Who is it for?: Ages 2 months to 17 years
Conditions the study is for: Grade B aGVHD, Grade C aGVHD, Grade D aGVHD
What is being tested?: remestemcel-L
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 55 participants
Where: 20 sitesUnited States
Study dates: 4 Jun 2015to 9 Apr 2018
Phase: Phase 3
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 months to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Participant is diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The participant may have Grade C or D aGVHD involving the skin, liver, and/or GI tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.
Participant has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D [International Bone Marrow Transplant Registry (IBMTR) grading] aGVHD that shows progression within 3 days, or no improvement within 7 days of consecutive treatment with 2 mg/kg/day methylprednisolone or equivalent.
Participant must be able to be treated with remestemcel-L within 4 days of signing of informed consent.
Participants who have had persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/kg/day (for participants >50 kg) or <30 mL/kg/day (for participants ≤50 kg). See GVHD Organ Severity Criteria (Table 2) for values in mL/m^2. In the absence of nausea or vomiting, participants could have been considered to have Grade B GVHD if:
other causes of diarrhea had been ruled out (eg, Clostridium difficile, adenovirus or cytomegalovirus [CMV] infection, or oral magnesium administration), and if
the low stool volume reflected the effects of fasting, narcotics, or antidiarrheal medications.

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Participant must have adequate renal function as defined by a calculated creatinine clearance of >30 mL/min per 1.73 m^2. For participants 1 to 18 years of age, creatinine clearance is calculated using the Bedside Schwartz equation:
Glomerular filtration rate (GFR, in mL/min per 1.73 m^2) = (0.413 height [cm])/serum creatinine (mg/dL)
For participants younger than 1 year of age, renal function is determined using the Schwartz equation adjusted for this age group:
Creatinine clearance (mL/min per 1.73 m^2= (height [cm] x 0.45)/ (serum creatinine [mg/dL]).
Participant has a minimum Karnofsky/Lansky 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.
Female participants of childbearing potential (≥10 years of age) are required to use a medically accepted method of contraception and to agree to continue use of this method for the duration of the study and for the follow-up time period. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
Male participants with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study, including the follow-up time period.
The participant must be willing and able to comply with study requirements, remain at the clinic, and return to the clinic for the follow-up evaluation during the study period, as specified in this protocol.

Who cannot join

Participant has Grade B aGvHD with skin-only involvement.
Participant has received any second line therapy to treat aGVHD prior to screening.
Participant has received systemic agents other than steroids and prophylactic agents for primary treatment of aGVHD.
Participant shows evidence of diffuse alveolar hemorrhage or other active pulmonary disease, which is likely to require more than 2L of oxygen via face mask, or an estimated fractional inspired oxygen concentration (FiO2) of 28% via other delivery methods in order to sustain an O2 saturation of 92%.
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 but not limited to uncontrolled infection, heart failure, or pulmonary hypertension.
Participant has received any stem cell agents (other than hematopoietic graft) during study participation or within 30 days prior to study entry. Previous use of irradiated granulocytes within 30 days is permitted.

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Participant has received an HSCT transplant for a solid tumor disease.
Participant has had prior treatment with mesenchymal stem cells (MSCs), including remestemcel-L.
Participant shows evidence of severe (required treatment) hepatic veno-occlusive disease (VOD) or sinusoidal obstruction at screening.
Participant had positive laboratory test results indicating infection with the human immunodeficiency virus (HIV) at any time and/or active hepatitis B or C virus infection within 3 months prior to screening.
Participant shows evidence of encephalopathy, as defined by a change in mental status since the onset of aGVHD.
Participant is a female who is pregnant, lactating, or is planning a pregnancy during study participation, or in the follow-up period.
Participant currently being treated for a solid tumor malignancy.
Participant has participated in any interventional clinical trial for an aGVHD therapeutic agent. However, in exceptional cases, experimental agents may have been administered to enrolled participants at the Investigator's discretion.
Participant has participated or is currently participating in any autologous and allogeneic stem cell or gene therapy study for the treatment of aGVHD. Participants participating in investigative protocols aimed at modification of the transplant graft (such as T-cell depletion) or aimed at modification of the conditioning regimen are allowed in the study.
Participant has a known hypersensitivity to dimethyl sulfoxide (DMSO) or to murine, porcine, or bovine proteins.

Trial locations and contacts

20 sites in 1 country.

City, postcode or hospital

20 sites in 1 country

United States20 sites

Children's Hospital Colorado Center for Cancer/Blood Disorders
Aurora, Colorado, 80045
Medical University of South Carolina
Charleston, South Carolina, 29425
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27705
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Hospital Los Angeles
Los Angeles, California, 90027
Miami Children's Research Institute
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10174
Albert Einstein College of Medicine
New York, New York, 10467
Children's Hospital of Orange County
Orange, California, 92868
Oregon University
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23284
Texas Transplant Institute
San Antonio, Texas, 78229
University of California at San Francisco
San Francisco, California, 94143
Fred Hutchinson Cancer Research
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63110
Alfred I. DuPont Hospital for Children of the Nemours Foundation
Wilmington, Delaware, 19803

Other trials in United States

About this study

Official title: A Single-arm, Prospective Study of Remestemcel-L, Ex-vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD

The study plans to treat at least 60 pediatric participants, male and female, between the ages of 2 months and 17 years inclusive with aGVHD following allogeneic hematopoietic stem cell transplant (HSCT) that has failed to respond to treatment with systemic corticosteroid therapy. Participants may have Grades C and D aGVHD involving the skin, liver and/or gastrointestinal (GI) tract or Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease.

Read the detailed description

Remestemcel-L will be evaluated in pediatric participants with aGVHD following allogeneic HSCT that has failed to respond to treatment with systemic corticosteroid therapy.

Conditions: Grade B aGVHD, Grade C aGVHD, Grade D aGVHD
Being tested: remestemcel-L
Keywords: GVHD

What participants receive

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

remestemcel-LDrug
Participants were treated with IV remestemcel-L at a dose of 2 x 10^6 MSC/kg (actual body weight at screening) twice per week for each of 4 consecutive weeks. Infusions were administered at least 3 days apart and no more than 5 days apart for any infusion.

Study groups in NCT02336230
Study group	Role	What they receive
Remestemcel-L 2×10^6 MSCs/kg	Experimental	Participants were treated with intravenous (IV) remestemcel-L at a dose of 2×10^6 mesenchymal stromal cells (MSCs)/kilogram (kg) actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening. Receives: Drug: remestemcel-L

What is being measured

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

Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy
ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.
Measured: Day 28

Secondary outcomes (5)

Overall Survival (OS) Rate at Day 100 Post Initiation of Therapy
Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.
Measured: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Responder Status at Day 28
Overall survival rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy.
Measured: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Baseline aGVHD Grade
OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. Maximum severity of acute GVHD was assessed by using International Bone Marrow Transplant Registry (IBMTR) index. The severity index was defined as: Grade A (skin Stage 1: extent of rash <25%); Grade B (skin Stage 2: extent of rash 25 to 50% or liver Stage 1 to 2: total bilirubin 34 to 102 micromoles per liter [mcmol/L] or intestinal tract Stage 1 to 2: volume of diarrhea 550 to 1500 milliliters per day [mL/day]); Grade C (skin Stage 3: extent of rash > 50% or liver Stage 3: total bilirubin 103 to 255 mcmol/L or intestinal tract Stage 3: volume of diarrhea >1500 mL/day); Grade D (skin Stage 4: extent of rash bullae or liver Stage 4: total bilirubin >255 or intestinal tract Stage 4: volume of diarrhea severe pain and ileus).
Measured: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Organ Involvement
OS rate was defined as percentage of participants who survived. OS was defined as the time to death from the start of drug therapy. The data was summarized for organ involvement: skin only, lower GI only, and multi-organ.
Measured: Day 100
OR Rate at Day 56 and 100 Post Initiation of Therapy
OR rate was defined as the percentage of participants who had achieved overall response. Overall response was defined as CR plus PR as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.
Measured: Day 56 and Day 100

Timeline

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

4 Jun 20159 Apr 2018

First posted12 Jan 2015 (estimated)
Study start4 Jun 2015
Primary completion9 Apr 2018
Study completion9 Apr 2018

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 Grade B aGVHDStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02336230
Sponsor's protocol ID: MSB-GVHD001
Status last verified: Feb 2022
First submitted: 30 Dec 2014
Last updated: 17 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Kurtzberg J, Abdel-Azim H, Carpenter P, Chaudhury S, Horn B, Mahadeo K, Nemecek E, Neudorf S, Prasad V, Prockop S, Quigg T, Satwani P, Cheng A, Burke E, Hayes J, Skerrett D; MSB-GVHD001/002 Study Group. A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 May;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018. Epub 2020 Feb 1.
PubMed 32018062

Study at a glance

From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-arm, Prospective Study of Remestemcel-L, Ex-vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD
ClinicalTrials.gov ID: NCT02336230
Acronym / sponsor ID: MSB-GVHD001
Conditions: Grade B aGVHD, Grade C aGVHD, Grade D aGVHD
Keywords: GVHD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: Mesoblast, Inc.Industry (pharma, biotech, devices)
Collaborators: Quintiles, Inc.
Study start: 4 Jun 2015 (actual)
Primary completion: 9 Apr 2018 (actual)
Study completion: 9 Apr 2018 (actual)
First posted: 12 Jan 2015 (estimated)
Results: Posted 17 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Remestemcel-L will be evaluated in pediatric participants with aGVHD following allogeneic HSCT that has failed to respond to treatment with systemic corticosteroid therapy.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Remestemcel-L 2×10^6 MSCs/kg	Experimental	Drug: remestemcel-LParticipants were treated with intravenous (IV) remestemcel-L at a dose of 2×10^6 mesenchymal stromal cells (MSCs)/kilogram (kg) actual body weight at Screening, twice per week, for each of 4 consecutive weeks (initial therapy) given at least 3 days apart and no more than 5 days apart for any infusion. Eligible participants received an additional once per week infusion, for each of 4 consecutive weeks (continued therapy) of remestemcel-L and twice per week infusions, for each of 4 consecutive weeks (aGVHD flare therapy) of remestemcel-L at the same initial therapy dose of 2×10^6 MSCs/kg actual body weight at Screening.

Who may qualify

Ages: 2 months to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (15 listed)

Participant is diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The participant may have Grade C or D aGVHD involving the skin, liver, and/or GI tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.
Participant has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D [International Bone Marrow Transplant Registry (IBMTR) grading] aGVHD that shows progression within 3 days, or no improvement within 7 days of consecutive treatment with 2 mg/kg/day methylprednisolone or equivalent.
Participant must be able to be treated with remestemcel-L within 4 days of signing of informed consent.
Participants who have had persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/kg/day (for participants >50 kg) or <30 mL/kg/day (for participants ≤50 kg). See GVHD Organ Severity Criteria (Table 2) for values in mL/m^2. In the absence of nausea or vomiting, participants could have been considered to have Grade B GVHD if:
Participant must have adequate renal function as defined by a calculated creatinine clearance of >30 mL/min per 1.73 m^2. For participants 1 to 18 years of age, creatinine clearance is calculated using the Bedside Schwartz equation:

Key exclusion criteria (16 listed)

Participant has Grade B aGvHD with skin-only involvement.
Participant has received any second line therapy to treat aGVHD prior to screening.
Participant has received systemic agents other than steroids and prophylactic agents for primary treatment of aGVHD.
Participant shows evidence of diffuse alveolar hemorrhage or other active pulmonary disease, which is likely to require more than 2L of oxygen via face mask, or an estimated fractional inspired oxygen concentration (FiO2) of 28% via other delivery methods in order to sustain an O2 saturation of 92%.
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 but not limited to uncontrolled infection, heart failure, or pulmonary hypertension.

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
remestemcel-LParticipants were treated with IV remestemcel-L at a dose of 2 x 10^6 MSC/kg (actual body weight at screening) twice per week for each of 4 consecutive weeks. Infusions were administered at least 3 days apart and no more than 5 days apart for any infusion.	Drug	Remestemcel-L 2×10^6 MSCs/kg

Primary outcome

Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy
Time frame: Day 28
ORR was defined as the percentage of participants who had achieved overall response. Overall response was defined as complete response (CR) plus partial response (PR) as per aGVHD response criteria. CR was defined as resolution of aGVHD in all involved organs. PR was defined as organ improvement of at least 1 stage without worsening of any other organ.

5 secondary outcomes

Overall Survival (OS) Rate at Day 100 Post Initiation of Therapy
Time frame: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Responder Status at Day 28
Time frame: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Baseline aGVHD Grade
Time frame: Day 100
OS Rate at Day 100 Post Initiation of Therapy, Stratified by Organ Involvement
Time frame: Day 100
OR Rate at Day 56 and 100 Post Initiation of Therapy
Time frame: Day 56 and Day 100

Results and safety

Results posted to the registry on 17 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Remestemcel-L 2×10^6 MSCs/kg	55	42

Primary outcome: Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy

Time frame: Day 28. Number. Unit: percentage of participants

Measure	Remestemcel-L 2×10^6 MSCs/kg n = 55
Value	69.1

Remestemcel-L 2×10^6 MSCs/kg: p = 0.0003, Binomial Distribution

Population analysed: FAS included all participants who provided informed consent, were screened, and were found eligible to enter the study.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Baseline through 100 days of follow up. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Remestemcel-L 2×10^6 MSCs/kg	35 of 54 (64.8%)	52 of 54 (96.3%)	13 of 55

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32018062Kurtzberg J, Abdel-Azim H, Carpenter P, Chaudhury S, Horn B, Mahadeo K, Nemecek E, Neudorf S, Prasad V, Prockop S, Quigg T, Satwani P, Cheng A, Burke E, Hayes J, Skerrett D; MSB-GVHD001/002 Study Group. A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 May;26(5):845-854. doi: 10.1016/j.bbmt.2020.01.018. Epub 2020 Feb 1.
Individual participant dataSharing planned: No

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 study director

Mesoblast, Inc.

20 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing remestemcel-L in people with Grade B aGVHD and Grade C aGVHD, run by Mesoblast, Inc. at 20 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 15 inclusion and 16 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 17 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 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 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?

Yes. Results are posted in the registry (first posted 17 Mar 2022). 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?

Overall Response Rate (ORR) at Day 28 Post Initiation of Therapy (time frame: Day 28). 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 NCT02336230, 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 17 Mar 2022; AzTrials last refreshed its copy on 8 Nov 2026.