Safety Follow-up of Treatment With Remestemcel-L in Pediatric Participants Who Have Failed to Respond to Steroid Treatment for Acute GVHD

• Sponsor: Mesoblast, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02652130
• Collaborator: Quintiles, Inc. (Industry)
• Enrollment: 32
• Locations: 20
• Arm: 1
• Actual Duration (Months): 31.6
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Ongoing safety assessment follow-up to Protocol MSB-GVHD001 (NCT02336230) of remestemcel-L treatment in pediatric participants with acute graft versus host disease (aGVHD), following allogeneic hematopoietic stem cell transplant (HSCT), that have failed to respond to treatment with systemic corticosteroid therapy.

Condition or Disease	Intervention/Treatment	Phase
Grade B Acute Graft Versus Host Disease; Grade C Acute Graft Versus Host Disease; Grade D Acute Graft Versus Host Disease	Biological: Remestemcel-L	Phase 3

Detailed Description

This is a safety follow-up study through 180 days of remestemcel-L treatment in participants who took part in MSB-GVHD001. This study will also explore duration of response over time. Participants who took part in in MSB-GVHD001 and received at least one dose of remestemcel-L as outlined in that protocol will be evaluated at baseline (Day 100) and at Days 120, 140, 160 and 180 for safety endpoints. Participants who took part in Protocol MSB-GVHD001 and received the first 8 doses of remestemcel-L as outlined in that protocol will be evaluated at baseline (Day 100) and at Days 120, 140, 160 and 180 after initial remestemcel-L infusion for evidence of duration of response over time.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Safety Follow-up Through 180 Days of Treatment With Remestemcel-L in Study MSB-GVHD001 in Pediatric Patients Who Have Failed to Respond to Steroid Treatment for Acute GVHD
• Actual Study Start Date: Oct 28, 2015
• Actual Primary Completion Date: Jun 15, 2018
• Actual Study Completion Date: Jun 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Safety population All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.	Biological: Remestemcel-L; No intervention was given in Study MSB-GVHD002 (NCT02652130). It was a safety follow-up trial of remestemcel-L-treated participants from Study MSB-GVHD001.

Outcome Measures

Primary Outcome Measures

1. Overall Survival Rate Through Day 180 [From Baseline Day 1 in the Study MSB-GVHD001 up to Day 180 in Study MSB-GVHD002 (180 days)]

   The overall survival rate is defined as the percentage of participants alive at the given time point. OS is defined as the time to death from the start of drug therapy.

Secondary Outcome Measures

1. Overall Survival Rate at Day 180 for Participants Who Had Overall Response (OR) at Day 28 of Study MSB-GVHD001 [From Baseline (Day 1) in the Study MSB-GVHD001 up to Day 180 in the Study MSB-GVHD002 (180 days)]

   The overall survival rate is defined as the percentage of participants alive at the given time point. OS is defined as the time to death from the start of drug therapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have participated in MSB-GVHD001 and have received at least one infusion of remestemcel-L.

• Participant or participant's authorized representative must be capable of providing written informed consent. Assent, if applicable, must also be collected when required by the Institutional Review Board (IRB)/Ethics Committee (EC).

• Female participants of childbearing potential (≥ 10 years of age) must use a medically accepted method of contraception and must 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.

• The participant must be willing and able to comply with study procedures, remain at the clinic as required during the study period, and return to the clinic for the follow-up evaluation as specified in this protocol.

Exclusion Criteria:

• The investigator believes it to be in the best interest of the participant not to participate in the safety follow-up study.

• Participant has participated or is currently participating in any autologous or 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 will be allowed in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	CHOC Children's Hospital of Orange County	Orange	California	United States	92868
3	UCSF Benioff Children's Hospital	San Francisco	California	United States	94143
4	Children's Hospital Colorado Center for Cancer/Blood Disorders	Aurora	Colorado	United States	80045
5	Alfred I. duPont Hospital for Children of the Nemours Foundation	Wilmington	Delaware	United States	19803
6	Miami Children's Research Institute	Miami	Florida	United States	33155
7	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
8	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
9	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
10	Washington University	Saint Louis	Missouri	United States	63110
11	Columbia University Medical Center	New York	New York	United States	10032
12	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10174
13	The Children's Hospital at Montefiore	New York	New York	United States	10467
14	Duke University Medical Center	Durham	North Carolina	United States	27705
15	Oregon Health & Science University	Portland	Oregon	United States	97239
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	Texas Transplant Institute	San Antonio	Texas	United States	78229
18	Virginia Commonwealth University	Richmond	Virginia	United States	23284
19	Fred Hutchinson Cancer Center	Seattle	Washington	United States	98109
20	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Mesoblast, Inc.
• Quintiles, Inc.

Investigators

• Study Director: Christopher James, Mesoblast, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 10, 2018

More Information

Publications

None provided.

• Responsible Party: Mesoblast, Inc.
• ClinicalTrials.gov Identifier: NCT02652130
• Other Study ID Numbers: MSB-GVHD002
• First Posted: Jan 11, 2016
• Last Update Posted: Mar 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mesoblast, Inc.: GVHD
• Additional relevant MeSH terms: Graft vs Host Disease; Remestemcel-l

Study Results

Participant Flow

Recruitment Details	54 participants enrolled in Study MSB-GVHD001 [NCT02336230], received >=1 dose of remestemcel-L; evaluated up to Day100. These participants were followed-up for OS, GVHD activity up to Day180 (end of Study MSB-GVHD002 [NCT02652130]). 32 of 54 participants were enrolled in Study MSB-GVHD002; evaluated at Baseline (Day 100) and at Days120, 140, 160 and 180.

Arm/Group Title	Remestemcel-L
Arm/Group Description	All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.
Period Title: Overall Study
STARTED	32
COMPLETED	31
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Remestemcel-L
Arm/Group Description	All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.
Overall Participants	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.8 (5.24)
Sex: Female, Male (Count of Participants)
Female	11 34.4%
Male	21 65.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 37.5%
Not Hispanic or Latino	20 62.5%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	20 62.5%
Black or African American	3 9.4%
Asian	2 6.3%
American Indian or Alaska Native	1 3.1%
Other	6 18.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival Rate Through Day 180
Description	The overall survival rate is defined as the percentage of participants alive at the given time point. OS is defined as the time to death from the start of drug therapy.
Time Frame	From Baseline Day 1 in the Study MSB-GVHD001 up to Day 180 in Study MSB-GVHD002 (180 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who signed the informed consent form and received at least one dose of study treatment (complete or partial) in the study MSB-GVHD001 and who signed the informed consent form for the study MSB-GVHD002 were followed across both the studies MSB-GVHD001 and MSB-GVHD002.

Arm/Group Title	Remestemcel-L
Arm/Group Description	All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.
Measure Participants	54
Number [percentage of participants]	68.5 214.1%

2. Secondary Outcome

Title	Overall Survival Rate at Day 180 for Participants Who Had Overall Response (OR) at Day 28 of Study MSB-GVHD001
Description	The overall survival rate is defined as the percentage of participants alive at the given time point. OS is defined as the time to death from the start of drug therapy.
Time Frame	From Baseline (Day 1) in the Study MSB-GVHD001 up to Day 180 in the Study MSB-GVHD002 (180 days)

Outcome Measure Data

Analysis Population Description

Duration of Response population included all participants who participated in Study MSB-GVHD001 and showed OR or very good partial response (VGPR) to remestemcel-L at Day 28 in Study MSB-GVHD001. The OS was evaluated across both Studies MSB-GVHD001 and MSB-GVHD002.

Arm/Group Title	Remestemcel-L
Arm/Group Description	All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.
Measure Participants	38
Number [percentage of participants]	78.9 246.6%

Adverse Events

Time Frame	Baseline (Day 100) up to Day 180 in Study MSB-GVHD002
Adverse Event Reporting Description	Safety population included all participants who signed the informed consent form and received at least one dose of study treatment (complete or partial) in Study MSB-GVHD001 and who signed the informed consent form for Study MSB-GVHD002. As no treatment was administered in this study, only serious adverse events are reported. Any non-serious treatment-emergent adverse events that occurred within 30 days of last treatment at the 5% threshold will be reported in Study MSB-GVHD001 [NCT02336230].
Arm/Group Title	Remestemcel-L
Arm/Group Description	All participants who were enrolled and had received at least 1 dose of remestemcel-L in Study MSB-GVHD001.
All Cause Mortality
	Remestemcel-L
	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)
Serious Adverse Events
	Remestemcel-L
	Affected / at Risk (%)	# Events
Total	15/32 (46.9%)
Blood and lymphatic system disorders
Febrile neutropenia	1/32 (3.1%)
Thrombocytopenia	1/32 (3.1%)
Gastrointestinal disorders
Pneumatosis intestinalis	1/32 (3.1%)
Haematochezia	1/32 (3.1%)
General disorders
Oedema peripheral	1/32 (3.1%)
Hepatobiliary disorders
Cholecystitis	1/32 (3.1%)
Infections and infestations
Pneumonia	2/32 (6.3%)
Septic shock	2/32 (6.3%)
Bacteraemia	1/32 (3.1%)
Bronchopulmonary aspergillosis	1/32 (3.1%)
Enterococcal infection	1/32 (3.1%)
Nocardiosis	1/32 (3.1%)
Osteomyelitis acute	1/32 (3.1%)
Pneumonia pneumococcal	1/32 (3.1%)
Pseudomonas infection	1/32 (3.1%)
Vulval abscess	1/32 (3.1%)
Injury, poisoning and procedural complications
Laceration	1/32 (3.1%)
Investigations
Weight decreased	1/32 (3.1%)
Metabolism and nutrition disorders
Hyperglycaemia	1/32 (3.1%)
Hypoalbuminaemia	1/32 (3.1%)
Hyponatraemia	1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Osteonecrosis	1/32 (3.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	1/32 (3.1%)
Post transplant lymphoproliferative disorder	1/32 (3.1%)
Skin and subcutaneous tissue disorders
Eczema	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Remestemcel-L
	Affected / at Risk (%)	# Events
Total	0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publications (abstracts, posters or presentations) must be presented to the Publication Steering Committee for review prior to submission or public display and are not allowed prior to the publication of the primary manuscript, or eighteen (18) months from the conclusion of the Study. PI shall provide Sponsor a copy of any proposed public disclosure at least 30 days prior to submission. Sponsor may ask PI to delay the disclosure for a maximum of 60 days to file proprietary protection.