MSB-GVHD001: A Single-arm, Prospective Study of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells, for the Treatment of Pediatric Patients who Have Failed to Respond to Steroid Treatment for Acute GVHD
Study ID: STU 122014-063
This trial will be a prospective, single-arm study involving multiple study centers, to evaluate the efficacy and safety of remestemcel-L in pediatric subjects with acute GVHD who have failed to respond to systemic steroid treatment. The study plans to treat at least 60 pediatric subjects, 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. Subjects 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. all subjects will be treated with intravenous (iV) remestemcel-L at a dose of 2 x 106 MSC per kg actual body weight at screening, twice per week for each of 4 consecutive weeks. Subject may continue to be treated with a stable dose of systemic steroid therapy until subject is able to be tapered and may contiue on an established dose of prophylactic therapy folling initiation of remestemcel-L. no other GVHD medications are to be introduced to subjects during the initail 28 days unless there is disease progression. if a secondary line agent is used prior to Day 28, this would constitute failure to respond. Progression of disease is defined as deterioration of GVHD by one or more grade from baseline assessment according to the definitions. GVHD assessments will be performed at screening and weekly until Day 100. a therapy assessment will be performed on Day 28 to determine treatment response and whether a subject will be provided continued treatment. eligible subjects will receive an additional 4 once-weekly infusions of remestemcel-L at the same initial dose, which will begin within one week after the Day 28 assessment. infusions will be given once weekly and must be administered within 28 days. no additional treatment with remestemcel-L is allowed at any other point in time unless the criterion for GVHD flare is met. The primary endpoint will be overall response (oR), defined as complete response (CR) or partial response (PR), of the study population at 28 days post initiation of therapy (Day 0) with remestemcel-L.
1.Subject was diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The subject may have Grade C or D aGVHD involving the skin, liver, and/or gastrointestinal (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. 2. Subject is 2 months to 17 years of age, inclusive 3. Subject has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D International Bone Marrow Transplant Registry (IBMTR) grading acute GVHD that shows progression within 3 days, or no improvement within 7 consecutive days, of treatment with 2 mg/kg/day methylprednisolone or equivalent. 4. Subject must be able to be treated with remestemcel-L within 4 days of study entry. 5. Subjects who have had persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/day (for subjects > 50 kg) or less than 30 mL/kg/day (for subjects <= 50 kg). In the absence of nausea or vomiting, subject may still be considered to have Grade B GVHD if: a) other causes of diarrhea have been ruled out (e.g., C. difficile, adenovirus or cytomegalovirus (CMV) infection, oral magnesium administration) and if b) the low stool volume reflects the effects of fasting, narcotics, or anti-diarrheal medications. 6. Subject must have adequate renal function as defined by a calculated creatinine clearance of >30 mL/min per 1.73 m2. For subjects 1 to 18 years of age creatinine clearance should be calculated using the Bedside Schwartz equation: GFR (ml/min per 1.73 m2) = [0.413 x height (cm)]/Serum creatinine (mg/dl) For subjects less than 1 year old, renal function should be determined using the Schwartz equation adjusted for this age group: Creatinine clearance (ml/min per 1.73 m2)= (height [cm] x 0.45)/ (serum creatinine [mg/dL]) 7. Subject has a minimum Karnofsky/Lansky Performance Level of 30 at the time of study entry 8. Subject (or legal representative where appropriate) must be capable of providing written informed consent. 9. Female subjects 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. Guidance on childbearing potential and pregnancy tests are located in Appendix 7 of the protocol. 10. Male subjects with partners of childbearing potential must agree to use adequate contraception (barrier method or abstinence) during the study, including the follow-up time period. 11. The subject must be willing and able to comply with study requirements, remain at the clinic, and be willing and able to return to the clinic for the follow-up evaluation, as specified in this protocol during the study period.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Victor Michael Aquino