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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Childr

Brief Summary: Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. This phase II trial is studying how well giving combination chemotherapy together with donor bone marrow or umbilical cord blood transplant works in treating children with newly diagnosed juvenile myelomonocytic leukemia

Detailed Summary:

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.

  • 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 ]


    • Original Primary Outcome:

    Current Secondary Outcome:

    • 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.


    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: October 11, 2001
    Date Started: June 2001
    Date Completion:
    Last Updated: April 10, 2013
    Last Verified: January 2013