Clinical Trial: Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized Phase II Study Comparing Two Different Conditioning Regimens Prior to Allogeneic Hematopoietic Cell Transplantation (HCT) for Children With Juvenile Myelomonocytic L

Brief Summary: This randomized phase II trial studies how well giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before donor hematopoietic cell transplant works in treating younger patients with juvenile myelomonocytic leukemia. Giving chemotherapy before a donor hematopoietic transplant helps stop the growth of cancer cells. It may also 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. It is not yet known whether giving busulfan, cyclophosphamide, and melphalan or busulfan and fludarabine phosphate before a donor stem cell transplant is more effective in treating juvenile myelomonocytic leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare - in a randomized fashion - the day 100 treatment related mortality (TRM) incidence for two myeloablative conditioning regimens, busulfan-fludarabine (fludarabine phosphate) (BU-FLU) and busulfan-cyclophosphamide-melphalan (BU-CY-MEL), prior to hematopoietic cell transplant (HCT) for children with juvenile myelomonocytic leukemia (JMML), in order to determine the preferred regimen for future trials.

II. To compare - in a randomized fashion - the 18-month event-free survival (EFS) following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML, in order to determine the preferred regimen for future trials.

SECONDARY OBJECTIVES:

I. To determine the 18-month relapse incidence (RI) following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML.

II. To determine the graft failure rates following two different myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL) prior to HCT for children with JMML.

TERTIARY OBJECTIVES:

I. To determine the rates of severe toxicities (grade 3/4) at day 100 post-HCT between the two myeloablative conditioning regimens (BU-FLU vs. BU-CY-MEL).

II. To determine the rates of acute and chronic (at 18 months post-HCT) graft-versus-host disease (GVHD) following HCT using two different conditioning regimens (BU-FLU vs. BU-CY-MEL) in children with JMML.

III. To create a JMML-specific pre-HCT index to allow better ris
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • EFS [ Time Frame: 18 months ]
    Will be estimated using the Kaplan-Meier method. An event is either TRM, primary or secondary graft failure, or relapse/non-response (as defined in protocol section 10). Time to event is time from transplant with patients who die between the start of the conditioning regimen and transplant given a time to event of zero.
  • TRM [ Time Frame: Day 100 ]
    Death prior to relapse or non-response. Time to TRM is defined as time from transplants to TRM. Patients who die between the start of the conditioning regimen and transplant will be considered a TRM with time to TRM of zero. Will be estimated as cumulative incidence using the Aalen-Johansen method.


Original Primary Outcome:

  • TRM [ Time Frame: Day 100 ]
    Will be estimated as cumulative incidence using the Aalen-Johansen method.
  • EFS [ Time Frame: 18 months ]
    Will be estimated using the Kaplan-Meier method.


Current Secondary Outcome:

  • Graft failure rates [ Time Frame: Up to 5 years ]
    Will be estimated using the cumulative incidence via the method of Aalen and Johannsen. Failure to achieve an ANC >= 500/uL after 42 days, determined by 3 consecutive measurements on different days; OR < 5% donor cells in blood or bone marrow by day +42 (as demonstrated by a chimerism assay), without evidence of JMML.
  • Relapse/non-response rates [ Time Frame: Up to 5 years ]
    As defined in protocol section 10. Will be estimated using the cumulative incidence via the method of Aalen and Johannsen.


Original Secondary Outcome:

  • Relapse/non-response rates [ Time Frame: Up to 5 years ]
    Will be estimated using the cumulative incidence via the method of Aalen and Johannsen.
  • Graft failure rates [ Time Frame: Up to 5 years ]
    Will be estimated using the cumulative incidence via the method of Aalen and Johannsen.


Information By: Children's Oncology Group

Dates:
Date Received: April 2, 2013
Date Started: June 2013
Date Completion: June 2022
Last Updated: January 11, 2017
Last Verified: January 2017