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

Alternate Title

Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	Child	NCI	COG-AAML0122 NCT00025038, AAML0122

Objectives

1. Determine the response rate of children with newly diagnosed juvenile myelomonocytic leukemia treated with R115777, isotretinoin, cytarabine, and fludarabine followed by allogeneic bone marrow or umbilical cord blood transplantation. (R11577 portion of the study closed to accrual as of 08/2005)
2. Determine the safety and toxicity of this regimen in these patients.
3. Determine the tolerability of this regimen in these patients.
4. Determine the rate of 2-year event-free survival of patients treated with this regimen.
5. Determine whether prognostic subsets of these patients can be identified based on expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic characteristics.

Entry Criteria

Disease Characteristics:

• Newly diagnosed, previously untreated juvenile myelomonocytic leukemia



• Presenting with all of the following:
  • Absence of t(9;22) or bcr/abl by PCR
  • Absolute monocyte count greater than 1,000/mm³
  • Less than 20% bone marrow blasts



• Presenting with at least 2 of the following:
  • Elevated F hemoglobin
  • Myeloid precursors in peripheral blood
  • WBC greater than 10,000/mm³
  • Sargramostim (GM-CSF) hypersensitivity

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No concurrent proton pump inhibitors

Patient Characteristics:

Age:

• Child

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT no greater than 3 times normal

Renal:

• Creatinine no greater than 2 times normal

Expected Enrollment

A maximum of 100 patients (18-46 receiving R115777 with induction chemotherapy [R11577 portion of the study closed to accrual as of 08/2005] and 27-54 receiving induction chemotherapy only) will be accrued for this study within 3.2 years.

Outcomes

Response rate
Safety and tolerability
Toxicity
Event-free survival at 2 years
Prognostic factors

Outline

This is a multicenter study.

Patients may choose to receive upfront window induction therapy with oral R115777 twice daily on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or stable disease with unacceptable hematopoietic recovery after 1 course proceed to induction chemotherapy. (R11577 portion of the study closed to accrual as of 08/2005)

All patients receive induction chemotherapy comprising oral isotretinoin once daily beginning on day 1 and fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5. Treatment with fludarabine and cytarabine repeats every 28 days for 2 courses. Treatment with isotretinoin continues until allogeneic bone marrow or umbilical cord blood transplantation. Patients with progressive disease after 1 course proceed to transplantation.

After completion of isotretinoin, patients receive a preparative regimen comprising total body irradiation twice daily on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 and -2, and anti-thymocyte globulin IV over 4-6 hours every 12 hours on days -3 to -1.

Patients undergo allogeneic bone marrow or umbilical cord blood transplantation on day 0. Patients receive oral isotretinoin daily beginning on approximately day 60 and continuing for 1 year.

Patients are followed every 6 months for 5 years and then annually thereafter.

Castleberry RP, Loh ML, Jayaprakash N, et al.: Phase II window study of the farnesyltransferase inhibitor R115777 (Zarnestra®) in untreated juvenile myelomonocytic leukemia (JMML): a Children’s Oncology Group Study. [Abstract] Blood 106 (11): A-2587, 2005.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Robert Castleberry, MD, Protocol chair		Ph: 205-939-9285; 800-822-0933 Email: rcastleberry@peds.uab.edu

Registry Information
Official Title		Phase II Window Evaluation of the Farnesyl Transferase Inhibitor (R115777) Followed by 13-CIS Retinoic Acid, Cytosine Arabinoside and Fludarabine Plus Hematopoietic Stem Cell Transplantation in Children with Juvenile Myelomonocytic Leukemia
Trial Start Date		2001-06-11
Registered in ClinicalTrials.gov		NCT00025038
Date Submitted to PDQ		2001-06-06
Information Last Verified		2006-10-20
NCI Grant/Contract Number		CA13539

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