Efficacy and Safety of Prochymal™ Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD - Full Text View

Sponsor:	Osiris Therapeutics
Information provided by:	Osiris Therapeutics
ClinicalTrials.gov Identifier:	NCT00562497

Purpose

This is a Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of Prochymal™ versus placebo in combination with corticosteroids as initial therapy for acute GVHD. Corticosteroids have been the primary therapy for patients with previously untreated acute GVHD and the historical published data define an expected 35% complete response (CR) at Day +28 using this therapy.

Condition	Intervention	Phase
Graft Versus Host Disease	Drug: Prochymal Other: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal™ Infusion in Combination With Corticosteroids for the Treatment of Newly Diagnosed Acute GVHD

Resource links provided by NLM:

Drug Information available for: Corticosteroids

U.S. FDA Resources

Further study details as provided by Osiris Therapeutics:

Primary Outcome Measures:

Achieved an induction of a complete response, Followed by 28 days of maintenance of a clinically meaningful response that does not did not require an increase in corticosteroid dose , did not require second line therapy and survived 90 days. [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response, Induction of a two grade decrease in GVHD and Maintenance, Induction of a CR lasting ≥14 days, Time to CR, Incidence of CR per organ, Total steroid dose through Day 90, Incidence of Steroid/Infectious complications [ Time Frame: 90 Days ] [ Designated as safety issue: No ]

Estimated Enrollment:	184
Study Start Date:	September 2007
Estimated Study Completion Date:	May 2010
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 2 Placebo	Other: Placebo Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all subjects receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.
Active Comparator: 1 Subjects assigned to the active treatment group will receive Prochymal™.	Drug: Prochymal Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the active treatment group will receive Prochymal™ at 2 x 106 hMSC/kg per infusion.

Arms

Assigned Interventions

Placebo Comparator: 2

Placebo

Other: Placebo

Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all subjects receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.

Active Comparator: 1

Subjects assigned to the active treatment group will receive Prochymal™.

Drug: Prochymal

Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the active treatment group will receive Prochymal™ at 2 x 106 hMSC/kg per infusion.

Detailed Description:

Subjects will be treated with a total of 6 infusions of investigational agent during the first 4 weeks of the study. Four infusions will be administered during the first two weeks (twice weekly), then two infusions administered during the next two weeks (once weekly). Subjects assigned to the active treatment group will receive Prochymal™. Subjects assigned to the non active treatment group will receive placebo (excipient, less cells). It is recommended that all subjects receive all six infusions. The discontinuation of investigational agent is allowed for GVHD worsening with subsequent need for salvage therapy. All infusions must be given at least 3 days apart.

Subjects will be evaluated for efficacy and safety until death, withdrawal or 90 study days after randomization, whichever occurs first. Study will be unblinded and data analyzed at Day 90 post 1st infusion (Day 0)following final subject enrollment. Subjects will be followed for safety for 12 months post 1st infusion (Day 0).

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects must be 18 years to 70 years of age, inclusive
Subjects must have received an allogeneic hematopoietic stem cell transplant using either bone marrow, peripheral blood stem cells or cord blood or administered a donor leukocyte infusion.
Subjects must have newly diagnosed Grades B-D acute GVHD. Biopsy confirmation of GVHD is strongly recommended but not required. Randomization should not be delayed awaiting biopsy or pathology results.
Subjects must be randomized and treated with corticosteroid (1-2 mg/kg/d methylprednisolone, or equivalent) and Prochymal™/placebo within 72 hours of onset of acute GVHD.
Subjects must have adequate renal function as defined by: Calculated Creatinine Clearance of >30mL/min using the Cockroft-Gault equation
Subjects who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male subjects must use adequate contraception
Subject must have a minimum Karnofsky Performance Level of at least 30 at the time of study entry
Subject (or legal representative where appropriate) must be capable of providing written informed consent.

Exclusion Criteria:

Subject has been previously treated with systemic immunosuppressive therapy for acute GVHD
Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension, etc.
Subjects may not receive any other investigational agents (not approved by the FDA for any indication) concurrently during study participation or within 30 days of randomization.
Subject has a known allergy to bovine or porcine products or DMSO
Subject has received a transplant for a solid tumor disease.
Subject requires more than 2L/min of oxygen to maintain stable SaO2 greater than or equal to 92%
Subject requires a renal dopamine dose greater than 1-3 mcg/kg/min to maintain renal blood flow associated with renal failure and improved urinary output.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00562497

Show 53 Study Locations

Sponsors and Collaborators

Osiris Therapeutics

Investigators

Study Director:

Rod L Monroy, Ph.D.

Osiris Therapeutics, Inc.

More Information

Additional Information:

Click here for more information about this study:A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Prochymal™ (Ex-vivo Cultured Adult Human Mesenchymal Stem Cells) Infusion in Combination with Corticos This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Rod Monroy, Osiris
ClinicalTrials.gov Identifier:	NCT00562497 History of Changes
Other Study ID Numbers:	265
Study First Received:	November 20, 2007
Last Updated:	August 26, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by Osiris Therapeutics:

Acute GVHD
Acute Graft Versus Host Disease

Additional relevant MeSH terms:

Graft vs Host Disease
Immune System Diseases

ClinicalTrials.gov processed this record on February 07, 2012