Safety and Efficacy Study of Adult Human Mesenchymal Stem Cells to Treat Acute Graft Versus Host Disease (GVHD)

NCT ID: NCT00136903

Last Updated: 2022-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-27

Study Completion Date

2008-07-14

Brief Summary

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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

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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

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Graft Vs Host Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Prochymal® - 2 Million cells/kg

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.

Group Type ACTIVE_COMPARATOR

Prochymal® - 2 Million cells/kg

Intervention Type DRUG

2 million hMSCs/kg actual body weight, IV on study Days 1 and 4

Methylprednisolone

Intervention Type DRUG

Methylprednisolone 2 mg/kg administered intravenously.

Prednisone

Intervention Type DRUG

Prednisone 2.5 mg/kg administered orally.

Cyclosporine

Intervention Type DRUG

Administered as prescribed by the caregiver.

Tacrolimus

Intervention Type DRUG

Administered as prescribed by the caregiver.

Mycophenolate Mofetil

Intervention Type DRUG

Administered as prescribed by the caregiver.

Prochymal® - 8 Million cells/kg

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.

Group Type ACTIVE_COMPARATOR

Prochymal®- 8 Million cells/kg

Intervention Type DRUG

8 million hMSCs/kg actual body weight IV on study Days 1 and 4

Methylprednisolone

Intervention Type DRUG

Methylprednisolone 2 mg/kg administered intravenously.

Prednisone

Intervention Type DRUG

Prednisone 2.5 mg/kg administered orally.

Cyclosporine

Intervention Type DRUG

Administered as prescribed by the caregiver.

Tacrolimus

Intervention Type DRUG

Administered as prescribed by the caregiver.

Mycophenolate Mofetil

Intervention Type DRUG

Administered as prescribed by the caregiver.

Interventions

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Prochymal® - 2 Million cells/kg

2 million hMSCs/kg actual body weight, IV on study Days 1 and 4

Intervention Type DRUG

Prochymal®- 8 Million cells/kg

8 million hMSCs/kg actual body weight IV on study Days 1 and 4

Intervention Type DRUG

Methylprednisolone

Methylprednisolone 2 mg/kg administered intravenously.

Intervention Type DRUG

Prednisone

Prednisone 2.5 mg/kg administered orally.

Intervention Type DRUG

Cyclosporine

Administered as prescribed by the caregiver.

Intervention Type DRUG

Tacrolimus

Administered as prescribed by the caregiver.

Intervention Type DRUG

Mycophenolate Mofetil

Administered as prescribed by the caregiver.

Intervention Type DRUG

Other Intervention Names

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Remestemcel-L ex-vivo cultured adult human mesenchymal stem cells hMSCs Remestemcel-L ex-vivo cultured adult human mesenchymal stem cells hMSCs

Eligibility Criteria

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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).

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mesoblast, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christopher James, PA

Role: STUDY_DIRECTOR

Mesoblast, Inc.

Locations

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St. Francis Hospital

Indianapolis, Indiana, United States

Site Status

Kansas City Cancer Centers - BMT

Kansas City, Missouri, United States

Site Status

The Cancer Center at Hackensack University

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Mt. Sinai Hospital

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Medical College of Wisconsin, FEC

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 11823036 (View on PubMed)

Deans 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.

Reference Type BACKGROUND
PMID: 10989188 (View on PubMed)

Lazarus 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.

Reference Type BACKGROUND
PMID: 15846293 (View on PubMed)

Le 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.

Reference Type BACKGROUND
PMID: 15121408 (View on PubMed)

Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. doi: 10.1080/14653240510018118.

Reference Type BACKGROUND
PMID: 16040382 (View on PubMed)

Kebriaei 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.

Reference Type RESULT
PMID: 19539211 (View on PubMed)

Related Links

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http://www.osiristx.com

Click here for more information on Prochymal® for treatment of GVHD

Other Identifiers

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260-261

Identifier Type: -

Identifier Source: org_study_id

NCT00476762

Identifier Type: -

Identifier Source: nct_alias

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