Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy (mylehaplo)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00796562
Recruitment Status : Completed
First Posted : November 24, 2008
Last Update Posted : December 14, 2016
Otsuka Pharmaceutical Co., Ltd.
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

November 20, 2008
November 24, 2008
December 14, 2016
November 2008
December 2016   (Final data collection date for primary outcome measure)
To estimate the incidence of donor cell engraftment following myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies. [ Time Frame: Day 14-60 ]
To estimate the incidence of graft rejection and severe graft versus-host disease (GVHD) following myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies [ Time Frame: Day 14-60 ]
Complete list of historical versions of study NCT00796562 on Archive Site
To estimate overall survival, relapse, non-relapse mortality, and event-free survival in patients receiving myeloablative conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives [ Time Frame: 2 years ]
Same as current
Not Provided
Not Provided
Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy
A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies
The purpose of this study is to see if giving high dose chemotherapy and total body irradiation before and repeating high dose chemotherapy after a bone marrow transplant could reduce the incidence of graft rejection and disease for patients with blood cancers

Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or nonmyeloablative conditioning, is a potentially curative treatment for a variety of hematologic malignancies and non-malignant hematologic disorders. Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and progression-free survival. Unfortunately, only about a third of candidates for alloBMT have HLA-matched siblings.

For patients who lack HLA-matched siblings, there are three alternative sources of stem cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical BMT has been associated with significant risks of graft rejection and severe GVHD, which are manifestations of excessive alloreactivity by host and donor T cells, respectively.

The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of mature T cells or selectively depleted of alloreactive T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic agent that has an established role in conditioning for alloBMT.

Typically, the drug is administered prior to transplantation to prevent graft rejection by suppressing the host immune system. However, pre-transplantation conditioning with Cy increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection and GVHD.

Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Screening
  • MDS
  • Leukemias
  • Lymphomas
  • Drug: Busulfan
    Patient will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis(in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.
  • Drug: Cyclophosphamide
    Patient will then receive Cy by IV once a day for 2 days.
    Other Names:
    • Cy
    • Cytoxan
    • CTX
  • Radiation: Total body irradiation
    Patients will receive TBI once a day for 4 days.
    Other Name: TBI
  • Active Comparator: Arm A
    All patients except those with acute lymphoblastic leukemias and lymphoblastic lymphomas. Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
    • Drug: Busulfan
    • Drug: Cyclophosphamide
  • Active Comparator: Arm B
    Patients with acute lymphocytic leukemia or lymphoblastic lymphoma. Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
    • Drug: Cyclophosphamide
    • Radiation: Total body irradiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2016
December 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Acute lymphocytic leukemia in high risk CR1
  • Acute myeloid leukemia in CR1
  • Therapy-related AML
  • RAEB with >5% and <20% bone marrow blasts
  • Chronic myelogenous leukemia beyond 1st chronic phase; Patients cannot be in blast crisis
  • CMMoL
  • JMML
  • Chemotherapy-resistant Hodgkins Lymphoma or intermediate or high grade Non-Hodgkins lymphoma (Less than a PR after standard or salvage chemotherapy)
  • Mantle cell lymphoma: chemotherapy refractory (Less than a PR after standard or salvage chemotherapy) or patients beyond CR1 with chemosensitive disease
  • Follicular Lymphoma, Grade 3
  • Transformed indolent lymphomas

Exclusion Criteria:

  • Poor cardiac function: left ventricular ejection fraction <45% as determined by MUGA or ECHO. For pediatric patients LVEF <45% or a shortening fraction below normal limits for age.
  • Poor pulmonary function: FEV1 and FVC <50% predicted for patients who have not received thoracic or mantle irradiation. For patients who have received thoracic or mantle irradiation, FEV1 and FVC <70% predicted or DLCO < 50 of predicted. For children unable to perform PFTs because of developmental stage pulse oximetry < 85% on RA
  • Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
  • Poor renal function: Creatinine >2.0mg/dl or creatinine clearance
  • HIV-positive
  • Positive leukocytotoxic crossmatch
  • Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
  • Uncontrolled viral, bacterial, or fungal infections Patients with symptoms consistent with RSV, influenza A, B, or parainfluenza at the time of enrollment will be assayed for the above viruses and if positive are not eligible for the trial until they are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms secondary to the nature of the assay.
  • Indolent lymphomas (Follicular Grade 1 and 2, marginal zone, chronic lymphocytic leukemia, small lymphocytic lymphoma, MALT)
Sexes Eligible for Study: All
6 Months to 65 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
NA_00015795 ( Other Identifier: JHH IRB )
KL2RR025006 ( U.S. NIH Grant/Contract )
Not Provided
Plan to Share IPD: No
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Otsuka Pharmaceutical Co., Ltd.
  • National Center for Research Resources (NCRR)
Principal Investigator: Heather Symons, M.D. Johns Hopkins University
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP