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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 December 2021
• Main ID: NCT02120157
• Date of registration: 16/04/2014
• Prospective Registration: Yes
• Primary sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Public title: Myeloablative Haploidentical BMT With Post-transplant Cyclophosphamide for Pediatric Patients With Hematologic Malignancies
• Scientific title: Pediatric Blood & Marrow Transplant Consortium (PBMTC) Phase II Myeloablative Haploidentical BMT With Post-transplantation Cyclophosphamide for Pediatric Patients With Hematologic Malignancies
• Date of first enrolment: July 2, 2015
• Target sample size: 35
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02120157
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, United States

Contacts

• Name: Heather Symons, MD, MHS
• Affiliation: SKCCC Johns Hopkins Hospital

Key inclusion & exclusion criteria

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



Age minimum: 6 Months
Age maximum: 25 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myeloablative Conditioning

Graft Survival

Transplantation, Bone Marrow

HLA-mismatched Bone Marrow Transplantation

Intervention(s)

Drug: Busulfan

Drug: Mycophenolate mofetil

Radiation: TBI

Drug: Tacrolimus

Other: Unmanipulated Bone Marrow

Drug: Cyclophosphamide

Primary Outcome(s)

Cumulative Incidence of Non-relapse Mortality [Time Frame: Day 180]

Secondary Outcome(s)

Steroid and Non-steroid Immunosuppressants [Time Frame: Two Years]

Immune Reconstitution [Time Frame: Two Years]

Incidence of Donor Cell Engraftment [Time Frame: 60 days]

Steroid and Non-steroid Immunosuppressants Use Duration [Time Frame: Two Years]

Survival [Time Frame: up to 1 years]

Primary and Secondary Graft Failure [Time Frame: 2 years]

Number of Participants With Donor Cell Engraftment [Time Frame: Day 60]

Survival [Time Frame: up to 2 years]

Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4 [Time Frame: 100 days]

Cumulative Incidence of Chronic GVHD [Time Frame: 2 years]

Time to Neutrophil and Platelet Recovery [Time Frame: 100 days]

Secondary ID(s)

J13161

NA_00091665

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02120157