Clinical trial NCT00509600: Etanercept (Enbrel) for Juvenile Myelomonocytic Leukemia
Official title: Phase IIA Window Study of Etanercept (Enbrel) for Juvenile Myelomonocytic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: Juvenile Myelomonocytic Leukemia
JMML
Leukemia
Etanercept
Enbrel
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2007-07-31
Enrollment: 1
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

1.1 Estimate rate of response and define acute toxicity to etanercept used in an up-front phase II window in newly diagnosed or relapsed JMML.

1.2 Determine if response to Tumor Necrosis Factor (TNF) blockade correlates with genetic basis of Juvenile Myelomonocytic Leukemia (JMML) \[mutations in NF1, Ras, SHP2\] or levels of TNFa.

1.3 Determine if TNF blockade by etanercept results in inhibition of free levels of TNFa and other cytokines by ELISA and bioassay and improves blood counts.

1.4 Estimate the two year event free survival and overall survival in JMML patients following etanercept and allogeneic hematopoietic stem cell transplantation.

Detailed description: Etanercept blocks a hormone called Tumor Necrosis Factor (TNF), which has been shown to play a role in helping the growth of leukemic cells in JMML.

Before participants can start treatment on this study, they will have what are called "screening tests". These tests will help the doctor decide if patients are eligible to take part in the study. You will have a complete medical history and physical exam. About two tablespoons of blood and urine will be collected for routine tests as well as to test for the liver and kidney function. You will have a bone marrow biopsy performed to monitor disease activity. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle. You will have cells from inside of the mouth tested for genetic changes by swabbing the side of the cheeks.

If you are found to be eligible, etanercept will be given as an injection under the skin once a week for up to 90 days.

During the study, you will have weekly follow-up tests that will include physical exam and lab tests. About 2 tablespoons of blood will be collected each time. Urine will also be collected for testing at least every 3 weeks while on the study.

If the disease gets worse or intolerable side effects occur, you will be taken off study and alternative treatment options will be discussed.

This is an investigational study. The FDA has approved etanercept for use in adults and children with rheumatoid arthritis and juvenile rheumatoid arthritis. Its use in this study is experimental. A total of up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility criteria: Inclusion Criteria:

1. All children greater than 6 months of age and less than 18 years of age with newly-diagnosed previously untreated or previously diagnosed JMML, which has reoccurred after treatment with chemotherapy, stem cell transplantation, and/or cis-retinoic acid.
2. A diagnosis of JMML is confirmed only if the following criteria for JMML are met: a) ALL of the following: Absence of t(9;22) or BCR-ABL by PCR or FISH; Absolute monocyte count \>1000 (1 X 109/µL); \<20% bone marrow blasts; b) At least 2 of the following: Elevated Hb F hemoglobin; Myeloid precursors in peripheral blood; WBC \>10,000 (10 X 109/µL); GM-CSF hypersensitivity in methylcellulose culture of bone marrow progenitors cells.
3. Adequate hepatic function (bilirubin equal or less than 2.0 mg/dl; ALT equal or less than 3x normal)
4. Adequate renal function (serum creatinine equal or less than 2 x normal)
5. Performance Status: Have a Karnofsky score \>50.
6. Written, informed consent according to institution guidelines.

Exclusion Criteria:

1. Pregnant or lactating.
2. Receiving any other chemotherapy. Patients must have been off chemotherapy for at least 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment.
3. Febrile neutropenia at study entry.

Primary outcomes:
measure: Patient Response
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD . Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Robert J. Wells, MD
role: PRINCIPAL_INVESTIGATOR
References: