Etanercept (Enbrel) for Juvenile Myelomonocytic Leukemia

This study has been terminated.
(Slow enrollment; study terminated.)
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00509600
First received: July 27, 2007
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Etanercept
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIA Window Study of Etanercept (Enbrel) for Juvenile Myelomonocytic Leukemia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Patient Response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Response is defined as a WBC < 15,000 and platelets > 75,000 at 12 weeks; toxicity is defined as a grade 3 or worse infection or non-hematologic toxicity within the first 4 weeks.


Enrollment: 1
Study Start Date: September 2004
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etanercept
0.8 mg/kg subcutaneously weekly for 90 days
Drug: Etanercept
0.8 mg/kg Subcutaneously Once A Week for 90 Days
Other Name: Enbrel

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

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509600

Locations
United States, Texas
UT MD . Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Amgen
Investigators
Principal Investigator: Robert J. Wells, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00509600     History of Changes
Other Study ID Numbers: 2004-0215
Study First Received: July 27, 2007
Results First Received: August 31, 2009
Last Updated: August 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Juvenile Myelomonocytic Leukemia
JMML
Leukemia
Etanercept
Enbrel

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
TNFR-Fc fusion protein
Immunoglobulin G
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 29, 2014