Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Lexatumumab With or Without Recombinant Interferon Gamma in Treating Young Patients With Solid Tumors or Lymphoma That Have Relapsed or Not Responded to Treatment

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Active	1 to 30	NCI	NCI-07-C-0040 NCI-P6981, NCT00428272

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Determine the tolerability of the adult maximum tolerated dose (MTD) and dose-limiting toxicities of lexatumumab in pediatric patients with relapsed or refractory solid tumors or lymphoma.
2. Determine the MTD of lexatumumab in combination with recombinant interferon gamma in these patients.
3. Assess the pharmacokinetics of this regimen in these patients.

Secondary

1. Quantify tumor response to this regimen in these patients.
2. Correlate immunohistochemical expression of pro-apoptotic proteins in pre-therapy tumor tissue with response in patients treated with this regimen.
3. Determine whether anti-lexatumumab antibodies are produced in response to this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignancy, including, but not limited to, any of the following:
  • Rhabdomyosarcoma and other soft tissue sarcoma
  • Ewing's sarcoma family of tumors
  • Osteosarcoma
  • Neuroblastoma
  • Wilms tumor
  • Hodgkin's lymphoma
  • Non-Hodgkin's lymphoma
• Measurable or evaluable disease
• Must have relapsed after or failed to respond to prior standard therapy
• No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
• No primary or metastatic hepatic tumors
• No primary or untreated metastatic CNS tumors
  • Patients with prior CNS metastases must meet the following criteria:
    • Metastases have been treated with surgery and/or radiotherapy
    • Clinically stable as evidenced by no requirement for corticosteroids
    • No evolving neurologic deficits and no change in residual brain abnormalities without specific therapy within the past 6 weeks

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior therapy
• At least 4 weeks since prior radiotherapy, chemotherapy, or monoclonal antibody therapy (6 weeks for nitrosoureas [e.g., lomustine or carmustine])
• At least 7 days since prior biological therapy or investigational therapy
• At least 72 hours since prior and no concurrent colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
• At least 3 months since prior autologous stem cell transplantation
• No prior allogeneic bone marrow transplantation
• No other concurrent immunotherapy or chemotherapy
• No concurrent immunosuppressant therapy (prednisone ≤ 10 mg/day or dexamethasone ≤ 4 mg/day allowed)
• No other concurrent investigational therapy

Patient Characteristics:

• Karnofsky performance status (PS) 50-100% (patients > 10 years of age) OR Lansky PS 50-100% (patients ≤ 10 years of age)
• Absolute granulocyte count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³ (transfusion independent)
• Hemoglobin ≥ 8 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Bilirubin (direct) normal
• Creatinine clearance ≥ 60 mL/min OR creatinine normal
• Ejection fraction > 40% by MUGA scan or ECHO OR shortening fraction > 27% by ECHO
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 60 days (females) or 30 days (males) after completion of study therapy
• No history of congestive heart failure
• No clinically significant unrelated systemic illness (e.g., serious infection or organ dysfunction) that would preclude study treatment
• No history of any infection requiring hospitalization or parenteral antibiotics within the past 2 weeks
• No co-existing medical illness that would place the patient at undue risk
• No known HIV infection
• No immune deficiency
• No hepatitis B or C

Expected Enrollment

A total of 68 patients will be accrued for this study.

Outcomes

Tolerability
Maximum tolerated dose of lexatumumab alone
Maximum tolerated dose of lexatumumab in combination with recombinant interferon gamma
Pharmacokinetics

Tumor response
Immunohistochemical expression of pro-apoptotic proteins in pre-therapy tumor tissue
Anti-lexatumumab antibody response

Outline

This is a multicenter, open-label, dose-escalation study of lexatumumab.

• Group I (lexatumumab alone): Patients receive lexatumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days until the maximum tolerated dose (MTD) is determined.
• Group II (lexatumumab and recombinant interferon gamma): Patients receive lexatumumab as in group I at the MTD. Patients also receive recombinant interferon gamma subcutaneously 3 times a week beginning on day -7 for 2 weeks and then once every 14 days until the MTD is determined. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically for pharmacokinetic studies. Blood serum is analyzed for concentration of lexatumumab via immunoenzyme techniques; anti-lexatumumab antibodies, TNF-related apoptosis-inducing ligand expression and caspase 8 expression, recombinant interferon gamma activity, lymphocyte storage, and immunogenicity via flow cytometry. Previously collected tissue samples are examined by immunohistochemistry for TR1, TR2, caspase 8, survivin, and bcl-2 expression.

After completion of study therapy, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Crystal Mackall, MD, Principal investigator		Ph: 301-402-5940

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Alexander Chou, MD	Ph:  212-639-8895 800-525-2225
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-2799

Registry Information
Official Title		A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors
Trial Start Date		2006-07-01
Registered in ClinicalTrials.gov		NCT00428272
Date Submitted to PDQ		2006-12-07
Information Last Verified		2008-04-15

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