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

Graft Vs Host Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00136903
• Other study ID #: 260-261
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2005
• Est. completion date: July 14, 2008

Study information

• Verified date: January 2022
• Source: Mesoblast, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Other known NCT identifiers

• NCT00476762

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 14, 2008
• Est. primary completion date: July 28, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft Vs Host Disease

Intervention

Drug:
• Prochymal® - 2 Million cells/kg
2 million hMSCs/kg actual body weight, IV on study Days 1 and 4
• Prochymal®- 8 Million cells/kg
8 million hMSCs/kg actual body weight IV on study Days 1 and 4
• Methylprednisolone
Methylprednisolone 2 mg/kg administered intravenously.
• Prednisone
Prednisone 2.5 mg/kg administered orally.
• Cyclosporine
Administered as prescribed by the caregiver.
• Tacrolimus
Administered as prescribed by the caregiver.
• Mycophenolate Mofetil
Administered as prescribed by the caregiver.

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The Cancer Center at Hackensack University	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	St. Francis Hospital	Indianapolis	Indiana
United States	Kansas City Cancer Centers - BMT	Kansas City	Missouri
United States	Medical College of Wisconsin, FEC	Milwaukee	Wisconsin
United States	Mt. Sinai Hospital	New York	New York
United States	University of Rochester	Rochester	New York
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Mesoblast, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. Review. — View Citation

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 B — View Citation

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. — View Citation

Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy. 2005;7(1):36-45. Review. — View Citation

Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Protocol 260 - Response by Day 28, also called Overall Response (OR). OR includes complete response (CR) and partial response (PR)		28 Days
Primary	Protocol 261-The incidence rate of different adverse events among participants treated with either dose of Prochymal® in the preceding study (Protocol No. 260).		2 Years
Secondary	Protocol 260 - Partial Response or Improvement of GVHD by Day 28 in one or more organs involved with GVHD symptoms at Day 1,		28 Days
Secondary	Protocol 260 - Time to best response of GVHD		28 Days
Secondary	Protocol 260 - Time to improvement of GVHD in one or more organs		28 Days
Secondary	Protocol 261 - Survival through study day 90		90 Days

External Links

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