We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies

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.
ClinicalTrials.gov Identifier: NCT02120157
Recruitment Status : Completed
First Posted : April 22, 2014
Results First Posted : April 18, 2019
Last Update Posted : November 26, 2021
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This is a multi-institutional phase II haploidentical T cell replete bone marrow transplant (BMT) study in children with high-risk leukemia. The myeloablative conditioning regimen prescribed will be Total body irradiation (TBI)-based for lymphoid leukemia and busulfan-based for myeloid leukemia. Our goal is to establish an easily exportable, inexpensive platform for haplotransplantation that has a safety profile equivalent to matched related and unrelated BMTs. The primary objective will be to estimate the incidence of 6-month non-relapse mortality (NRM), hypothesizing that NRM is < 18%.

Condition or disease Intervention/treatment Phase
Myeloablative Conditioning HLA-mismatched Bone Marrow Transplantation Graft Survival Transplantation, Bone Marrow Drug: Cyclophosphamide Radiation: TBI Drug: Busulfan Other: Unmanipulated Bone Marrow Drug: Tacrolimus Drug: Mycophenolate mofetil Phase 2

Detailed Description:

This is a phase II prospective study designed to evaluate the incidence of 6 month non- relapse mortality, safety, and feasibility of haploidentical bone marrow transplantation (BMT) after myeloablative conditioning with post-transplant Cy. Conditioning regimens include a total body irradiation (TBI)-based prep for lymphoid leukemias and a chemotherapy based prep for myeloid leukemias.

To estimate the incidence of non-relapse mortality at 180 days following myeloablative haploidentical BMT for children and young adults with high risk hematologic malignancies.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies
Actual Study Start Date : July 2, 2015
Actual Primary Completion Date : June 15, 2018
Actual Study Completion Date : October 1, 2020

Arm Intervention/treatment
Experimental: Haploidentical BMT with PTCy for acute leukemias and MDS

Patients with AML and MDS:

Days -6 through -3: Busulfan q 5-6h IV q24h x 4 days

Days -2 and -1: Cyclophosphamide 50mg/kg/day IV x 2 days+ Mesna 40 mg/kg/day IV

For patients with ALL and lymphoblastic lymphoma:

Days -5 through -4: Cyclophosphamide 50mg/kg/day IV q24h x 2 days+Mesna 40 mg/kg/day IV

Days -3 through -1: TBI 200 Centigray (cGy) twice a day for 3 days

All patients Day 0: Infuse unmanipulated bone marrow

Day +3 and +4: Cyclophosphamide 50 mg/kg/day IV + Mesna 40 mg/kg IBW/day IV

Day +5: Begin tacrolimus 0.015mg/kg IBW/dose IV over 4 hours q 12h and mycophenolate mofetil (MMF)15mg/kg po/IV tid with maximum daily dose 3 gm/day

Day +30: Assess chimerism and disease status in bone marrow

Day +35: Discontinue MMF

Day +60: Assess chimerism and disease status in bone marrow

Day 180: Discontinue tacrolimus

Drug: Cyclophosphamide
Chemotherapy administration
Other Name: Cy

Radiation: TBI
Radiation Therapy

Drug: Busulfan
Chemotherapy Administered
Other Name: Bu

Other: Unmanipulated Bone Marrow
Bone Marrow Transplant

Drug: Tacrolimus
Immunosuppressive Drug Administered
Other Name: tacro

Drug: Mycophenolate mofetil
Immunosuppressive Drug Administered
Other Name: MMF

Primary Outcome Measures :
  1. Cumulative Incidence of Non-relapse Mortality [ Time Frame: Day 180 ]
    Cumulative incidence (measured as a percentage) of non-relapse mortality at 180 days following myeloablative, Human Leukocyte Antigen (HLA)-mismatched bone marrow transplant (BMT) for patients with high risk hematologic malignancies.

Secondary Outcome Measures :
  1. Number of Participants With Donor Cell Engraftment [ Time Frame: Day 60 ]
    Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.

  2. Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4 [ Time Frame: 100 days ]
    Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).

  3. Cumulative Incidence of Chronic GVHD [ Time Frame: 2 years ]
    Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).

  4. Primary and Secondary Graft Failure [ Time Frame: 2 years ]
    Incidence (measured as a percentage) of primary and secondary graft failure.

  5. Steroid and Non-steroid Immunosuppressants [ Time Frame: Two Years ]
    Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.

  6. Steroid and Non-steroid Immunosuppressants Use Duration [ Time Frame: Two Years ]
    Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.

  7. Survival [ Time Frame: up to 1 years ]
    Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 1 year. Incidence as a percentage.

  8. Survival [ Time Frame: up to 2 years ]
    Estimate incidence of overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), event-free survival, and relapse-free GVHD-free survival (GRFS) in patients receiving myeloablative, HLA-mismatched BMT for patients with high risk hematologic malignancies at 2 years. Incidence as a percentage.

  9. Immune Reconstitution [ Time Frame: Two Years ]
    Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).

  10. Time to Neutrophil and Platelet Recovery [ Time Frame: 100 days ]
    Time to neutrophil and platelet recovery in median days

  11. Incidence of Donor Cell Engraftment [ Time Frame: 60 days ]
    Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   6 Months to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient age 0.5-25years
  • Patients must have a first-degree related donor or half-sibling who is at minimum HLA haploidentical. The donor and recipient must be identical at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
  • An unrelated donor search is not required for a patient to be eligible for this protocol, or a donor search and donor mobilization may be abandoned if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant or a low-likelihood of finding a matched, unrelated donor. Patients with an eligible HLA-matched RELATED should not be enrolled on this trial.
  • Patients must have at least one of the following high-risk conditions listed below:
  • Acute lymphocytic leukemia (ALL) in CR1* as defined by at least one of the following:

hypodiploidy, induction failure,Minimal residual disease (MRD) after consolidation

- Acute myeloid leukemia (AML) in CR1 with high risk features defined as: High allelic ratio FLT3/ITD+, Monosomy 7, Del (5q), Standard risk cytogenetics with positive minimal residual disease at the end of Induction I chemotherapy (for patients being treated on or according to Children's Oncology Group (COG) AAML1031 study who have had MRD studies sent to Seattle or performed at their local institution where the flow assay is sensitive enough to detect > 0.1% blasts)

  • Acute Leukemia in 2nd or subsequent CR (CR>2)
  • Mixed phenotype/Undifferentiated Leukemia in 1st or subsequent CR*
  • Secondary or therapy related leukemia in CR > 1
  • Natural Killer (NK) cell lymphoblastic leukemia CR > 1
  • Myelodysplastic syndrome (MDS)
  • Juvenile myelomonocytic leukemia (JMML) (patients are eligible if they are not eligible for COG1221 study)
  • Prior transplant eligible if < 18yo, >6 months has elapsed since BMT, and patient is off immunosuppression for > 3 months with no Graft versus host disease (GVHD)
  • No known active Central nervous system (CNS) involvement or extramedullary involvement by malignancy. Such disease treated into remission is permitted.
  • Acute Leukemia - Remission is defined as morphology with < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity.

Exclusion Criteria:

  • Poor cardiac function: left ventricular ejection fraction <45% as determined by Multigated acquisition scan (MUGA) or Echocardiogram (ECHO). For pediatric patients Left ventricular ejection fraction (LVEF) <45% or a shortening fraction below normal limits for age.
  • Symptomatic pulmonary disease. Poor pulmonary function: Forced expiratory volume (FEV1), Forced vital capacity (FVC), and Diffusing capacity for carbon monoxide (DLCO) <50% predicted (corrected for hemoglobin) 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 Pulmonary function tests (PFTs) because of developmental stage pulse oximetry < 92% on Room air (RA).
  • Poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy). Alanine aminotransferase (ALT) or Aspartate transaminase (AST) > 3 x laboratory upper normal limits.
  • Poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 60 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl) Multiply by another factor of 0.85 if female Intended for ages 18-110, serum creatinine 0.6-7 mg/dl For patients <18 years: creatinine clearance (CrCl) will be estimated by the Schwartz formula. A measured CrCl or a Glomerular filtration rate (GFR) may be substituted to determine the subject's CrCl.
  • Schwartz equation: CrCl (ml/min/1.73m2)=[length (cm) x k] /serum creatinine K = 0.45 for infants 1 to 52 weeks old k = 0.55 for children 1 to 13 years old k = 0.55 for adolescent females 13-18 years old k = 0.7 for adolescent males 13-18 years old
  • HIV-positive
  • Positive leukocytotoxic crossmatch Specifically, complement dependent cytotoxicity and flow cytometric crossmatch assays must be negative, and the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay should be <3000. Consult with PI for the clinical significance of any anti-donor antibody.
  • Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception or who are breastfeeding
  • Uncontrolled viral, bacterial, or fungal infections (currently taking medication and have progression of clinical symptoms)
  • Patients with symptoms consistent with Respiratory syncytial virus (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120157

Layout table for location information
United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, Delaware
Nemours Alfred I. DuPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Florida
All Children's Hospital Johns Hopkins Medicine
Saint Petersburg, Florida, United States, 33701
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Levine Cancer Center
Charlotte, North Carolina, United States, 28203
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29423
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Layout table for investigator information
Principal Investigator: Heather Symons, MD, MHS SKCCC Johns Hopkins Hospital
  Study Documents (Full-Text)

Documents provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02120157    
Other Study ID Numbers: J13161
NA_00091665 ( Other Identifier: JHM IRB )
First Posted: April 22, 2014    Key Record Dates
Results First Posted: April 18, 2019
Last Update Posted: November 26, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Acute lymphoblastic leukemia
Acute myeloid leukemia
Juvenile myelomonocytic leukemia
Treatment related leukemia
Biphenotypic leukemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents