Pharmacokinetics-based Mycophenolate Mofetil Dosing for GVHD Prevention

NCT01487577 | Completed Phase 2 Results DMC

• 1 other identifier: CHP_BMT_MMF_10
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Bone marrow transplantation (BMT) is used to successfully treat high-risk forms of leukemia, lymphoma, and other childhood cancers that were once considered incurable. A major barrier to the application of this life-saving treatment is acute graft-versus-host disease (GVHD) which develops in approximately 30-80% of patients and is a leading cause of death from transplant complications. Current GVHD prevention methods are not very efficacious and lead to unacceptable side effects. Mycophenolate mofetil (MMF), an anti-rejection medication used in solid organ transplants, has shown great promise in BMT recipients. The effectiveness of MMF depends on blood levels of mycophenolic acid (MPA, the active form of MMF). Different patients have been found to have different blood levels of MPA when they are given the same dose of MMF. The purpose of this study is to study a novel method of giving MMF based on its metabolism (pharmacokinetics) to achieve desired blood levels of MPA for prevention of GVHD. Non-invasive ways of monitoring the drug exposure will also be studied. The ultimate goal of this study is to improve approaches to GVHD prevention and improve outcomes of BMT in children.

Conditions

Allogeneic Blood and Marrow Transplantation (BMT); Graft Versus Host Disease

Keywords

Allogeneic blood and marrow transplantation (BMT); Graft versus host disease; Mycophenolate mofetil; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Grade ≥3 Toxicities Scored According to the CTCAE Version 4.0.

  100 days

• Number of Participants With Acute Grade II-IV GVHD, Acute Grade III-IV GVHD, and Chronic GVHD.

  Acute GVHD will be graded according to the Modified Glucksberg Staging Criteria. Chronic GVHD will be graded according to NIH Chronic GVHD Consensus Guidelines.

  1 year

Secondary Outcomes (7)

• Number of Participants With Neutrophil and Platelet Engraftment.

  100 days

• Number of Participants Who Experienced Relapse.

  1 year

• Number of Participants Who Experienced Nonrelapse Mortality.

  1 year

• Number of Participants in Overall Survival.

  1 year

• Pharmacokinetic Analysis of MMF AUC to Evaluate MMF Dose Relationships to Drug Exposure.

  100 days

Study Arms (1)

Mycophenolate mofetil

EXPERIMENTAL

Pharmacokinetics-based targeting of mycophenolate mofetil

Drug: Mycophenolate mofetil

Interventions

Mycophenolate mofetil DRUG

Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Also known as: Cellcept, MMF

Mycophenolate mofetil

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be between 6 months and 21 years of age.
• Recipients of an allogeneic blood and marrow transplant (BMT).
• Stem cell sources should be bone marrow or umbilical cord blood.
• Bone marrow or cord blood unit: Sibling should be HLA matched at A, B and DRB1 loci. Unrelated cord blood unit should be at a minimum 4/6 matched at allele level on HLA A, B and DRB1 loci. Unrelated donor should be HLA allele level matched at A, B, C and DRB1 loci.
• Minimum prefreezing nucleated cell dose for cord blood units: 3x10\^7/kg for malignant diseases and 5x10\^7/kg for nonmalignant diseases.
• Conditioning regimen must be myeloablative in intensity. Examples include but are not limited to Cy/TBI, BuCy 200, etc.
• Patients ≥ 16 years old must have a Karnofsky score ≥ 70%, and patients \< 16 years old must have a Lansky score ≥ 70%.
• Renal: Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2.
• Hepatic: Total bilirubin ≤ 2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase \< 5 x upper limit of normal (ULN) for age.
• Cardiac: Left ventricular ejection fraction at rest \> 40%, or shortening fraction \> 26%, by echocardiogram or radionuclide scan.
• Pulmonary: FEV1, FVC, and DLCO (diffusion capacity) \> 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation \> 92% of room air.

You may not qualify if:

• Patients with a known hypersensitivity to MMF.
• Prior autologous or allogeneic BMT \< 12 months prior to enrollment.
• Mismatched related donor.
• Mismatched unrelated marrow donor.
• Peripheral blood stem cell source.
• Reduced intensity conditioning.
• Uncontrolled bacterial, viral, fungal or other infection.
• Evidence of HIV infection or HIV positive serology.
• Requirement of supplemental oxygen.
• Patients who are pregnant (B-hCG positive) or breastfeeding. All females of 11 years of age or older and/or who have begun menstruating will be screened for hCG by either urinalysis or a blood sample in order to screen for pregnancy status, as per institutional BMT policy.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Limitations and Caveats

Our study is limited by small sample size and heterogeneity in stem cell sources. Besides targeted MMF dosing, other factors that might have affected clinical outcomes include duration of MMF and use of ATG in unrelated-donor transplants.

Results Point of Contact

• Title: Randy M. Windreich, MD
• Organization: Children's Hospital of Pittsburgh of UPMC

randy.windreich@chp.edu

412-692-5225

Study Officials

• Randy M Windreich, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 23, 2011
• First Posted: December 7, 2011
• Study Start: June 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: January 1, 2016
• Last Updated: June 21, 2016
• Results First Posted: June 21, 2016

Record last verified: 2016-05

Locations

US (1)