A multicenter phase II study to evaluate a safety and efficacy of the clofarabine combination chemotherapy for infants with newly diagnosed MLL gene rearranged ALL and an exploratory study for infants with germline MLL gene ALL (MLL-17)
A study of clofarabine combination therapy for infant ALL (MLL-17)
A patient must meet all of the following criteria in order to be eligible to participate in MLL-17 study:
(1) Infants less than 365 days of age at time of diagnosis of acute lymphoblastic leukemia (ALL)
(2) Patients with newly diagnosed ALL.
(3) A written informed consent of CHM-14 must be obtained prior to the registration of MLL-17.
(4) A written informed consent of MLL-17 registration must be obtained from the parents or guardians.
A patient who meets any of the following criteria will be excluded from participation in MLL-17 study:
(1) If patients are diagnosed at < 30 days of age, patients gestational age is less than 36 weeks and 0 days
(2) T-ALL, presence of t(9;22) (q34;q11) or BCR-ABL fusion transcript, presence of t(8;14)(q24;q32), t(2;8)(p13;q24), t(8;22)(q24;q11) or specific fusion transcript associated with mature B-ALL, and Down syndrome associated ALL
* Mature B-ALL without 8q24/MYC rearrangement, mixed phenotype acute leukemia (MPAL), and acute leukemia of ambiguous lineage (ALUL) will be included in this clinical trial.
(3) Patients who evaluated as ECOG Performance status (PS) score 4 which revised for infants.
(4) Patients with unacceptable severe organ failure
a. Patients with uncontrollable severe cardiac failure
b. Patients with uncontrollable severe renal failure
c. Patients with respiratory failure who need ventilatory support
d. Patients with unacceptable severe central nerve system hemorrhage
(5) Patients with uncontrollable severe infection.
(6) Patients with severe congenital disease or unacceptable complications
(7) Patients with double cancer
(8) Receipt of steroid pretreatment, prior cytotoxic chemotherapy and radiation therapy
(9) Patients who evaluated ineligible by principal physician
(1) Any Grade 5 toxicity (CTCAE ver 4.0)
(2) Adverse events occurring during CLARA (Clofarabine and cytarabine chemotherapy) treatment phase which delay more than 4 weeks of next chemotherapy
(3) Unacceptable grade 4 severe toxicity during CLARA treatment phase
(4) Hematological CR rate and MRD positive rate of timepoint 2 and timepoint 3
(5) Remission rate after induction chemotherapy
(6) Time to treatment failure
(7) Overall survival period
(8) Event free survival (EFS)
(9) Cumulative recurrence rates
(10) Non-relapse mortality
(11) Positive rate of PCR-MRD, FCM-MRD, and NGS-MRD at each timepoint
(12) Pharmacokinetic (PK) testing of clofarabine in infants
(13) Incidence of clinically relevant toxicities more than grade 3 (CTCAE ver4.0)
(14) Treatment completion rate
(15) Evaluation of quality of life for patients evaluated by families
(16) Complication on 100th day, 1st year, and 2nd year after stem cell transplantation
(17) Incidence of severe RSV infection
(18) Incidence of invasive fungal infection
(19) Incidence of sepsis
(20) Incidence of severe viral infection during maintenance therapy
(21) Immune function during maintenance therapy
(22) Overall survival and event free survival rate according to treatment for patients who showed PCR-MRD positive at TP4
(23) Evaluation of immune function during maintenance therapy (IR)
(24)Evaluation of immune function during maintenance therapy (LR)
(25) Incidence of silent inactivation of L-asparaginase.
(26) OS, EFS and incidence of adverse events related L-asparaginase according to the silent inactivation of L-asparaginase.
(27) Correlation of silent inactivation of L-asparaginase and anti-L-asparaginase antibody.
(28) Correlation between NUDT15 gene polymorphisms and 3-year EFS
(29) Correlation between NUDT15 gene polymorphisms and hematological toxicities (>= grade 3) during maintenancetherapy.