Therapy resitant leukemia in children and young adults
Conditions
Interventions
Trade Name: Evoltra
Product Name: Clofarabine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ETOPOSIDE PHOSPHATE
CAS Number: 117091642
Current Sponsor code: Etoposid
O
Sponsors
Skånes University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 3.1 Inclusion Criteria I. Target population 1. Refractory acute lymphoblastic leukemia a. Chemoresistant isolated or combined bone marrow relapse • Relapse after during/after conventional treatment • Relapse >6 months after allogeneic stem cell transplantation b. Primary induction failure c. Isolated extramedullary relapse after previous HSCT (>6 months) 2. Refractory acute myeloblastic leukemia including sAML a. Chemoresistant relapse • Relapse after during/after conventional treatment • Relapse >6 months after allogeneic stem cell transplantation[1] b. Primary induction failure II. Inclusion criteria to start induction treatment with multidrug regimen 1. Age > 1 and =21 years 2. Patients with previous HCST = 6 m[1] 3. Provide signed written informed consent patients’, and patients’ parents/guardians a. 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 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys. • Serum bilirubin =1.5 × upper limit of normal (ULN) • Aspartate transaminase (AST)/alanine transaminase (ALT) =2.5 × ULN • Alkaline phosphatase = 2.5 × 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. III. 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 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys. • Serum bilirubin =1.5 × upper limit of normal (ULN) • Aspartate transaminase (AST)/alanine transaminase (ALT) =2.5 × ULN • Alkaline phosphatase = 2.5 × 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 enrolment. 7. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Are the trial subjects under 18? yes Number of subjects for this age r
Exclusion criteria
Exclusion criteria: 3.2 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.2 Primary Objectives a) To improve event free survival for children with acute leukemia resistant to conventional therapy using “bridge to transplant” approach b) To demonstrate graft versus leukemia effect in children with therapy resistant leukemia who underwent haploidentical stem cell transplantation with subsequent cell therapy (DLI);Secondary Objective: 1.3 Secondary Objectives a) Evaluation of induction efficacy measured by response rate and the number of children proceeding to transplant b) Tolerance, safety and quality of life c) To evaluate hematological and immunological recovery ;Primary end point(s): 1) The number of patients "bridged to transplant" with CLoEC induction 2) Overall survival day +100 and day +365 after stem cell transplantation 3) Event free survival day +100 and +365 after stem cell transplantation 4) Disease free survival day +100 and day +365 after stem cell transplantation 5) Incidence of garft versus host disease. 6) Immunological recovery | — |
Countries
Sweden
Outcome results
None listed