- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00025038
Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia
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
Study Overview
Status
Conditions
Intervention / Treatment
- Other: laboratory biomarker analysis
- Drug: fludarabine phosphate
- Drug: tipifarnib
- Drug: cyclophosphamide
- Drug: cytarabine
- Drug: isotretinoin
- Biological: anti-thymocyte globulin
- Radiation: radiation therapy
- Procedure: allogeneic bone marrow transplantation
- Procedure: double-unit umbilical cord blood transplantation
- Procedure: umbilical cord blood transplantation
Detailed Description
PRIMARY OBJECTIVES:
I. 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.
II. Determine the safety and toxicity of this regimen in these patients. III. Determine the tolerability of this regimen in these patients. IV. Determine the rate of 2-year event-free survival of patients treated with this regimen.
V. Determine whether prognostic subsets of these patients can be identified based on expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic characteristics.
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.
PROJECTED ACCRUAL: 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
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Arcadia, California, United States, 91006-3776
- Children's Oncology Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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/mm^3
- 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/mm^3
- Sargramostim (GM-CSF) hypersensitivity
- See Disease Characteristics
- Bilirubin no greater than 2.0 mg/dL
- ALT no greater than 3 times normal
- Creatinine no greater than 2 times normal
- No concurrent sargramostim (GM-CSF)
- No concurrent proton pump inhibitors
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
|
Correlative studies
Given IV
Other Names:
Given orally
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given orally
Other Names:
Given IV
Other Names:
Undergo total body irradiation
Other Names:
Undergo allogeneic bone marrow transplant
Other Names:
Undergo allogeneic cord blood transplant
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate (CR or PR)
Time Frame: Up to 6 years
|
The response rates in the up-front window with respect to whether or not patients had vas activating mutations will also be estimated by proportions.
|
Up to 6 years
|
Duration of response
Time Frame: Up to 6 years
|
Will be estimated by Kaplan-Meier method.
|
Up to 6 years
|
Progression-free survival
Time Frame: 2 years
|
Will be estimated by Kaplan-Meier method.
|
2 years
|
Evaluation of prognostic importance of genetic marker
Time Frame: Up to 6 years
|
Logrank test and Cox proportional hazards model will be applied.
|
Up to 6 years
|
Grade 3 or greater toxicities assessed using CTC version 2.0
Time Frame: Up to 6 years
|
Up to 6 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Survival of patients receiving the window vs. not
Time Frame: Up to 6 years
|
Up to 6 years
|
|
Response status on end of course reports (pre vs.post)
Time Frame: Up to 6 years
|
Signed-rank comparison of components of therapy will be done.
|
Up to 6 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Robert Castleberry, Children's Oncology Group
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Myeloid
- Leukemia
- Leukemia, Myelomonocytic, Acute
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Cyclophosphamide
- Immunoglobulins
- Fludarabine
- Fludarabine phosphate
- Cytarabine
- Tipifarnib
- Thymoglobulin
- Antilymphocyte Serum
- Isotretinoin
Other Study ID Numbers
- NCI-2012-01861
- U10CA098543 (U.S. NIH Grant/Contract)
- AAML0122
- CDR0000068788 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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