Clinical trial NCT05827549: Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia
Official title: Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoid Leukemia
Keywords: combination chemotherapy
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Samsung Medical Center
name: Seoul National University Hospital
name: Severance Hospital
name: Chonnam National University Hospital
name: Pusan National University Yangsan Hospital
name: Seoul St. Mary's Hospital
First posted: 2023-04-25
Enrollment: 90
Sex: ALL
Minimum age (years): 1
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is open-label, multi-center, prospective study, which targets childhood patients with relapsed acute lymphostatic leukemia including bone marrow recurrence. Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for relapsed acute lymphoblastic leukemia in children and adolescents.

Detailed description: The Risk Assessment is classified as follows based on the NGS-MRD results evaluated after EOI(End of Induction).

\<Standard Risk\>

* Late (Relapse ≥ 1 year after off treatment) B-ALL marrow or Combined relapse AND
* End of induction MRD \< 0.01%

\<High Risk\>

* T-ALL marrow or combined relapse (any timing)
* All other B-ALL marrow or combined relapse cases

\<Very High Risk\>

• End of Induction BM ≥ M2 AND B -ALL marrow or combined relapse

Eligibility criteria: Inclusion Criteria:

* Patients \<= 1 year and \>22 years of age at the time of relapse will be eligible
* Participants must have a histologic diagnosis of acute lymphoblastic leukemia:

  * B-ALL: Precursor B-cell acute lymphoblastic leukemia
  * T-ALL: Precursor T-cell acute lymphoblastic leukemia
* 1st recurred acute lymphoblastic leukemia patients, recurred parts including marrow. Enrolling patients with combined extra medullary relapse including bone marrow is acceptable. (No limits for extra medullary site) Additionally, subjects whose blast cells in bone marrow are less than 5% (ALL whether type M2 or M3 must be definite)
* Patients who have never received allogeneic stem cell transplant
* Patients who have never received blinatumomab before
* Adequate Renal Function

  -A serum creatinine based on age/gender as follows:

  1 to \&lt; 2 years - Male (0.6) Female (0.6) 2 to \&lt; 6 years - Male (0.8) Female (0.8) 6 to \&lt; 10 years - Male (1) Female (1) 10 to \&lt; 13 years - Male (1.2) Female (1.2) 13 to \&lt; 16 years - Male (1.5) Female (1.4)

  ≥ 16 years - Male (1.7) Female (1.4)
* Adequate Liver Function defined as a direct bilirubin \&lt;3.0 mg/dL
* Adequate Cardiac Function defined as: Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by echocardiogram
* Lansky (age \&lt; 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60% at screening
* Patients with a life expectancy of 1 or more year
* Patients who are expected to comply with all required study procedures and follow the study protocol in the opinion of the investigator
* Signed written informed consent and assent forms must be obtained prior to any study procedures

Exclusion Criteria:

* Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
* Patients with Philadelphia chromosome positive (Ph+) ALL
* Patients with CD19-negative recurrent progenitor B-cell acute lymphoblastic leukemia (non-expression of CD19 in peripheral blood or bone marrow by flow cytometry) are not eligible for administration of Blinatumomab
* In case of relapsed within 1 month after the end of induction with the same 4-drug therapy used in this study
* Patients with mixed phenotype leukemia
* patient who was relapsed within 1 month after the end of induction therapy with the same 4-drug regimen to be used in this study.
* Patients with genetic syndrome: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome bone marrow failure syndrome
* Patients with known HIV
* Female patients who are not proved as infertile or pregnant (Evidence of infertility: History taking of possibilities of pregnancy or urine human chorionic gonadotrophin test negative, amenorrhea more than a year, Natural or artificial (Ex.hormone therapy) menopause status more than a year, surgical sterilization(Ex.Hysterectomy or ovariotomy etc)
* Currently receiving treatment in another investigational drug study or clinical trial
* Evidence of unstable conditions that would pose a risk to subject safety or interfere with the patients\&#39; compliance
* Patients with clinically relevant central nervous system (CNS) pathology or active CNS involvement including: unstable epilepsy, uncontrolled seizure, paralysis, aphasia, history of severe brain injury, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder
* Known hypersensitivity to drugs or components to be administered: Idarubicin, Etoposide, Ifosfamide, Cytarabine, Vincristine, Mercaptopurine, Blinatumomab

Primary outcomes:
measure: Safety/Efficacy
timeFrame: through study completion, an average of 9 year
Secondary outcomes:
measure: Disease-free survival rate (Blinatumomab)
timeFrame: through study completion, an average of 9 year
measure: Disease-free survival rate (standard risk)
timeFrame: through study completion, an average of 9 year
measure: Disease-free survival rate (Comparing minimal residual disease)
timeFrame: through study completion, an average of 9 year
measure: Death rate related to treatment
timeFrame: through study completion, an average of 9 year
measure: Death rate related to toxicity
timeFrame: through study completion, an average of 9 year
measure: Toxicity rate during consolidation therapy
timeFrame: through study completion, an average of 9 year
Other outcomes:
Locations:
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul saint Mary's Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Asan Medical Center
name: Ho Joon Im
role: STUDY_CHAIR
References: