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NCT02120157 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2021-11-26

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%.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Cumulative Incidence of Non-relapse Mortality

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outcome · POSTED

Number of Participants With Donor Cell Engraftment

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outcome · POSTED

Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4

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outcome · POSTED

Cumulative Incidence of Chronic GVHD

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outcome · POSTED

Primary and Secondary Graft Failure

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outcome · POSTED

Steroid and Non-steroid Immunosuppressants

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outcome · POSTED

Steroid and Non-steroid Immunosuppressants Use Duration

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outcome · POSTED

Survival

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outcome · POSTED

Survival

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outcome · POSTED

Immune Reconstitution

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outcome · POSTED

Time to Neutrophil and Platelet Recovery

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outcome · POSTED

Incidence of Donor Cell Engraftment

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
25 Years
minimum Age
6 Months
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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
    intervention Names
    1. Drug: Cyclophosphamide
    2. Radiation: TBI
    3. Drug: Busulfan
    4. Other: Unmanipulated Bone Marrow
    5. Drug: Tacrolimus
    6. Drug: Mycophenolate mofetil
    label
    Haploidentical BMT with PTCy for acute leukemias and MDS
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Chemotherapy administration
    name
    Cyclophosphamide
    other Names
    1. Cy
    type
    DRUG
  2. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Radiation Therapy
    name
    TBI
    type
    RADIATION
  3. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Chemotherapy Administered
    name
    Busulfan
    other Names
    1. Bu
    type
    DRUG
  4. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Bone Marrow Transplant
    name
    Unmanipulated Bone Marrow
    type
    OTHER
  5. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Immunosuppressive Drug Administered
    name
    Tacrolimus
    other Names
    1. tacro
    type
    DRUG
  6. arm Group Labels
    1. Haploidentical BMT with PTCy for acute leukemias and MDS
    description
    Immunosuppressive Drug Administered
    name
    Mycophenolate mofetil
    other Names
    1. MMF
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
35
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Cumulative Incidence of Non-relapse Mortality
    time Frame
    Day 180
secondary Outcomes
  1. description
    Number of Participants with Donor Cell Engraftment at Day 60 following myeloablative, HLA-mismatched BMT.
    measure
    Number of Participants With Donor Cell Engraftment
    time Frame
    Day 60
  2. description
    Cumulative incidence (measured as a percentage) of acute GVHD grades 2-4 (overall) and grades 3-4 (severe).
    measure
    Cumulative Incidence of Acute Graft Versus Host Disease (GVHD) Grades 2-4 and Grades 3-4
    time Frame
    100 days
  3. description
    Cumulative incidence (measured as a percentage) of chronic graft versus host disease (GVHD).
    measure
    Cumulative Incidence of Chronic GVHD
    time Frame
    2 years
  4. description
    Incidence (measured as a percentage) of primary and secondary graft failure.
    measure
    Primary and Secondary Graft Failure
    time Frame
    2 years
  5. description
    Number of participants who used steroid and non-steroid immunosuppressants to treat GVHD.
    measure
    Steroid and Non-steroid Immunosuppressants
    time Frame
    Two Years
  6. description
    Duration of use of steroid and non-steroid immunosuppressants (in months) to treat GVHD.
    measure
    Steroid and Non-steroid Immunosuppressants Use Duration
    time Frame
    Two Years
  7. description
    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.
    measure
    Survival
    time Frame
    up to 1 years
  8. description
    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.
    measure
    Survival
    time Frame
    up to 2 years
  9. description
    Characterize immune reconstitution post myeloablative haploidentical BMT with Post transplantation cyclophosphamide (PT/Cy).
    measure
    Immune Reconstitution
    time Frame
    Two Years
  10. description
    Time to neutrophil and platelet recovery in median days
    measure
    Time to Neutrophil and Platelet Recovery
    time Frame
    100 days
  11. description
    Incidence of donor cell engraftment measured as the percentage of donor cell engraftment.
    measure
    Incidence of Donor Cell Engraftment
    time Frame
    60 days
Full study description
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%.
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.
Source references
references
  1. citation
    Fierro-Pineda JC, Tsai HL, Blackford A, Cluster A, Caywood E, Dalal J, Davis J, Egeler M, Huo J, Hudspeth M, Keating A, Kelly SS, Krueger J, Lee D, Lehmann L, Madden L, Oshrine B, Pulsipher MA, Fry T, Symons HJ. Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias. Blood Adv. 2023 Sep 26;7(18):5639-5648. doi: 10.1182/bloodadvances.2023010281.
    pmid
    37257193
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice