Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia

Acute Lymphoid Leukemia Clinical Trial

— ReCALL  

Official title:

Evaluation of Treatment Efficacy According to Risk Group in Relapsed Childhood Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05827549
• Other study ID #: KPHOG_T1RALL2201
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: December 31, 2032

Study information

• Verified date: March 2024
• Source: Asan Medical Center
• Contact: Ho Joon Im, Professor
• Phone: +82-2-3010-3371
• Email: hojim[@]amc.seoul.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is open-label, multi-center, prospective study, which targets childhood patients with recurred acute lymphostatic leukemia including recurrence around marrow. This study is designed to administer Idarubicin for Reinduction stage. Patients with recurrence are sorted into groups with their potential risk, and depending on their recurrence point, time, reaction to treatment etc, they are sorted into low-risk group, high-risk group, and highest-risk group.

Patients with high-risk group are going to be given blinatumomab at consolidation stage before hematopoietic stem cell transplantation.

Patients with low-risk group who are not suitable for hematopoietic stem cell transplantation are going to be maintaining maintenance therapy for 2 years for chemotherapy.

Description:

1. Baseline demographics: Sex, Birth date, expire date (last follow-up date for the survivals)

2. Diagnosis of Acute lymphoblastic leukemia and treatment history: Diagnosed date, treatment history (Stem cell transplantation history, Administration of Blinatumomab history, recurrence date to check whether recurred within a month after received 4 therapies of induction)

3. Tests before actual administration: EKG and or Echo, Blood sample: Complete Blood Count/Diff/Platelets, Chemistry, Urinalysis, HIV, human chorionic gonadotrophin [female], Minimal Residual Disease[Next-generation sequencing, after induction / could be done after 1st, 2nd consolidation therapy]

4. Bone marrow aspiration

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: December 31, 2032
• Est. primary completion date: December 31, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 22 Years

Eligibility

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 < 2 years - Male (0.6) Female (0.6) 2 to < 6 years - Male (0.8) Female (0.8) 6 to < 10 years - Male (1) Female (1) 10 to < 13 years - Male (1.2) Female (1.2) 13 to < 16 years - Male (1.5) Female (1.4)

= 16 years - Male (1.7) Female (1.4)

• Adequate Liver Function defined as a direct bilirubin <3.0 mg/dL

• Adequate Cardiac Function defined as: Shortening fraction of = 27% by echocardiogram, or Ejection fraction of = 50% by echocardiogram

• Lansky (age < 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

• 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 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' 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

Related Conditions & MeSH terms

• Acute Lymphoid Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Blincyto
Vincristine 1.5mg/m2, L-asparaginase 6,000 IU/m2 Idarubicin 10mg/m2 will be administered for induction therapy. Ifosfamide 1.8g/m2 Etoposide 100mg/m2 will be administered for consolidation therapy, then patients will be sorted into groups depend on their potential risk and Blinatumomab IV will be administered over 28 days. Intensification course will be administered 4 times repeated. 1. etoposide 100mg/m2 Ifosfamide 3.4g/m2 with MESNA / 2.oral 6-mercaptopurine 50mg/m2, methotrexate 25mg/m2 / 3.Ara-C 1.0g/m2, Idarubicin 5mg/m2 / 4.vincristine 2mg/m2 are the courses for repetition.

Locations

Country	Name	City	State
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Gangnam-gu
Korea, Republic of	Seoul National University Hospital	Seoul	Jongro-gu
Korea, Republic of	Severance Hospital	Seoul	Gangnam-gu
Korea, Republic of	The Catholic University of Korea Seoul St.Mary's Hospital	Seoul	Gangnam-gu

Sponsors (1)

Lead Sponsor	Collaborator
Ho Joon Im

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/Efficacy	Patients with relapsed acute lymphoblastic leukemia are being treated after sorted into groups with their potential risk, and disease-free survival rate will be checked.	through study completion, an average of 9 year
Secondary	Disease-free survival rate (Blinatumomab)	Blinatumomab is used before transplantation to patients with high-risk group, and then disease-free survival rate will be compared before and after	through study completion, an average of 9 year
Secondary	Disease-free survival rate (standard risk)	Patients with standard risk who are not eligible for allogenic stem cell transplantation are given consolidation and maintenance therapies, and disease-free survival rate will compared before and after	through study completion, an average of 9 year
Secondary	Disease-free survival rate (Comparing minimal residual disease)	Comparing minimal residual disease negative rate with the study before by adding blinatumomab to patients in high risk group	through study completion, an average of 9 year
Secondary	Death rate related to treatment	Children and adolescents who have relapsed acute lymphoblastic leukemia re administered different treatments depending on their assigned groups, and disease-free survival rate will be compared before and after	through study completion, an average of 9 year
Secondary	Death rate related to toxicity	Comparing remission rate and occurrence rate of toxicity during re-intervention therapy after changed schedules of idarubicin	through study completion, an average of 9 year
Secondary	Toxicity rate during consolidation therapy	Checking occurence rate of toxicity related to treatment during consolidation for patients in low-risk group	through study completion, an average of 9 year