Mifamurtide (L-MTP-PE) for High-Risk Osteosarcoma

• ClinicalTrials.gov Identifier: NCT00631631
• Recruitment Status: Completed
• First Posted: March 10, 2008
• Last Update Posted: May 14, 2014
• Sponsor: Millennium Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Millennium Pharmaceuticals, Inc.

Study Description

Brief Summary:

The purpose of this study was to collect information regarding the safety and tolerability of mifamurtide (liposomal muramyl tripeptide phosphatidyl ethanolamine; L-MTP-PE).

Condition or disease	Intervention/treatment
Osteosarcoma	Drug: Mifamurtide (L-MTP-PE)

Detailed Description:

The drug being tested in this study is called mifamurtide (L-MTP-PE; liposomal muramyl tripeptide phosphatidyl ethanolamine). Mifamurtide is being used to treat people with osteosarcoma, a form of cancer.

This was a patient-access study that looked at adverse events, disease progression, and overall survival in study participants.

The study enrolled 205 patients, of whom 204 were treated with mifamurtide intravenously at a dose of 2 mg/m2 twice weekly (at least 3 days apart) for 12 weeks, and then weekly for an additional 24 weeks, for a total of 48 doses in 36 weeks (following surgery for primary or metastatic disease).

This study was conducted in the United States. Participants could receive treatment for up to 9 months. This study was previously mis-categorized as an interventional study.

Study Design

• Study Type: Observational
• Actual Enrollment: 205 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Liposomal Muramyl Tripeptide Phosphatidyl Ethanolamine (L-MTP-PE) for High-risk Osteosarcoma
• Study Start Date: January 2008
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Groups and Cohorts

Group/Cohort	Intervention/treatment
Mifamurtide (L-MTP-PE); Mifamurtide (L-MTP-PE), intravenous, at a dose of 2 mg/m^2 twice weekly (at least 3 days apart) for 12 weeks, and then weekly for an additional 24 weeks, for a total of 48 doses in 36 weeks.	Drug: Mifamurtide (L-MTP-PE); Solution for intravenous infusion; Other Name: Liposomal Muramyl Tripeptide Phosphatidyl Ethanolamine

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events [ Time Frame: 12 months or disease progression, whichever occurs first ]

Secondary Outcome Measures :

1. Serum concentration-time profiles of free and total mifamurtide in 15-20 patients [ Time Frame: Just before the start of the first infusion of mifamurtide and at 0.5, 1, 2, 4, 6 and, 24 hours following the start of the first infusion and just prior to the 2nd dose of mifamurtide ]
2. Overall survival [ Time Frame: From date of enrollment to date of death ]
3. Progression-free survival [ Time Frame: From date of enrollment to date of first documented disease progression or death ]

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Had diagnosis of high grade osteosarcoma with relapsed or recurrent disease, locally or metastatic, with disease not completely resectable or who were unable to complete recommended chemotherapy due to toxicity: relapse, recurrence local or metastatic; unable to have standard surgical resection; abbreviated chemotherapy regimen secondary to toxicity.

Criteria

Inclusion Criteria:

1. Had signed informed consent/assent. Voluntary participation in the pharmacokinetic portion of the compassionate access protocol was included in the informed consent but not required for compassionate use participation.
2. Had diagnosis of high grade osteosarcoma with relapsed or recurrent disease, locally or metastatic, with disease not completely resectable or who were unable to complete recommended chemotherapy due to toxicity: relapse, recurrence local or metastatic; unable to have standard surgical resection; abbreviated chemotherapy regimen secondary to toxicity (e.g. hypophosphatemia from ifosfamide, cardiotoxicity from doxorubicin, renal dysfunction from methotrexate, ifosfamide, or cisplatin.)
3. Aged 2 ≤ 50 years.
4. Had adequate hematopoietic function as demonstrated by: 1) Absolute Neutrophil Count (ANC) > 750/microL; Hemoglobin (Hb) > 8 g/dL; Platelets > 30,000/microL.
5. Had adequate hepatic function as documented by 1) ALT < 2.5 x upper limit of normal (ULN) for age; 2) total bilirubin ≤ 1.5 x ULN for age.
6. Had adequate renal function as demonstrated by: 1) Creatinine clearance or radioisotope glomerular filtration rate > 70 mL/min/1.73 m^2; OR, 2) Serum creatinine ≤ 2x ULN for age.
7. Had absence of concurrent active acute infection (i.e., afebrile).
8. In females of child bearing potential (not menopausal for 12 months or no previous surgical sterilization), had a negative pregnancy test. All sexually active participants used an effective means of contraception. Such means included oral contraceptives, Lupron Depot, DepoProvera, and condom with diaphragm and spermicidal jelly.
9. Performance status: Lansky 50-100% (≤ 16 years of age); OR, Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky 50-100% (>16 years of age).

Exclusion Criteria:

1. Had chronic use of corticosteroids or other immunosuppressive agents.
2. Was pregnant or breast-feeding.

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Texas

U.T.M.D. Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Peter M. Anderson, MD, PhD; M.D. Anderson Cancer Center

More Information

• Responsible Party: Millennium Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00631631
• Other Study ID Numbers: MTP-OS-403
• First Posted: March 10, 2008
• Last Update Posted: May 14, 2014
• Last Verified: May 2014

Keywords provided by Millennium Pharmaceuticals, Inc.:

Drug Therapy

Additional relevant MeSH terms:

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Mifamurtide; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs