Haploidentical Stem Cell Transplantation for Children With Therapy Resistant Leukemia

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Haploidentical hematopoietic stem cell transplantation, Graft versus host disease, Donor lymphocyte infusion, Graft versus leukemia effect, Immunological recovery, Bridge to transplant approach, Therapy resistant leukemia, Hematological malignancy Read More

Inclusion Criteria:

Target population

1. Refractory acute lymphoblastic leukemia

   • Chemoresistant isolated or combined bone marrow relapse

     • Relapse after during/after conventional treatment
     • Relapse ≥6 months after allogeneic stem cell transplantation
   • Primary induction failure
   • Isolated extramedullary relapse after previous HSCT (>6 months)

2. Refractory acute myeloblastic leukemia including sAML

   • Chemoresistant relapse

     • Relapse after during/after conventional treatment
     • Relapse ≥6 months after allogeneic stem cell transplantation
   • Primary induction failure

Inclusion criteria to start induction treatment with multidrug regimen

1. Age ≥ 1 and ≤21 years
2. Patients with previous HCST ≥ 6 m

3. Provide signed written informed consent patients', and patients' parents /guardians

   • Older children should be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent as well.
4. Cardiac output SF ≥25%

5. Have adequate renal and hepatic functions as indicated by the following laboratory values:

   • Calculated creatinine clearance ≥90 ml/min/1.73 m2
   • Serum bilirubin ≤1.5 X upper limit of normal (ULN)
   • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
   • Alkaline phosphatase ≤ 2.5 X ULN
6. Performance score of ≥70% (Lansky or Karnofsky)
7. A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
8. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Inclusion criteria to proceed to transplant after induction

1. Cardiac output SF ≥25%

2. Have adequate renal and hepatic functions as indicated by the following laboratory values:

   • Calculated creatinine clearance ≥90 ml/min/1.73 m2
   • Serum bilirubin ≤1.5 X upper limit of normal (ULN)
   • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
   • Alkaline phosphatase ≤ 2.5 X ULN
3. Performance score of ≥70% (Lansky or Karnofsky)
4. A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
5. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
6. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
7. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.

2. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea.

   The patient must have recovered from all acute toxicities from any previous therapy.

3. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
4. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
5. Pregnant or lactating patients.
6. Any significant concurrent malignant disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.