Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia
|ClinicalTrials.gov Identifier: NCT00025038|
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : April 11, 2013
|Condition or disease||Intervention/treatment||Phase|
|Juvenile Myelomonocytic Leukemia||Drug: tipifarnib Drug: isotretinoin Drug: fludarabine phosphate Drug: cytarabine Radiation: radiation therapy Drug: cyclophosphamide Biological: anti-thymocyte globulin Procedure: allogeneic bone marrow transplantation Procedure: double-unit umbilical cord blood transplantation Procedure: umbilical cord blood transplantation Other: laboratory biomarker analysis||Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||June 2001|
|Actual Primary Completion Date :||October 2007|
Experimental: Treatment (tipifarnib, bone marrow/umbilical cord transplant)
See detailed description.
Drug: fludarabine phosphate
Radiation: radiation therapy
Undergo total body irradiation
Biological: anti-thymocyte globulin
Procedure: allogeneic bone marrow transplantation
Undergo allogeneic bone marrow transplant
Procedure: double-unit umbilical cord blood transplantation
Procedure: umbilical cord blood transplantation
Undergo allogeneic cord blood transplant
Other: laboratory biomarker analysis
- 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.
- Duration of response [ Time Frame: Up to 6 years ]Will be estimated by Kaplan-Meier method.
- Progression-free survival [ Time Frame: 2 years ]Will be estimated by Kaplan-Meier method.
- Evaluation of prognostic importance of genetic marker [ Time Frame: Up to 6 years ]Logrank test and Cox proportional hazards model will be applied.
- Grade 3 or greater toxicities assessed using CTC version 2.0 [ Time Frame: Up to 6 years ]
- Survival of patients receiving the window vs. not [ Time Frame: 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00025038
|United States, California|
|Children's Oncology Group|
|Arcadia, California, United States, 91006-3776|
|Principal Investigator:||Robert Castleberry||Children's Oncology Group|