Multicenter prospective clinical trial for high-risk neuroblastoma patients with additional chemotherapy, and KIR ligand mismatched allogeneic cord blood transplantation for the poor prognosis group (JCCG-JN-H-20)
Clinical trial for neuroblastoma patients with additional chemotherapy and KIR ligand mismatched allogeneic cord blood transplantation
Koh Katsuyoshi
3-6-35 Nishiki, Naka-ku, Nagoya
+81-52-734-2182
office@jccg.jp
Takahashi Yoshiyuki
Nagoya University Hospital
65 Tsurumai-cho, Showa-ku, Nagoya, Aichi
+81-52-744-2298
ytakaha@med.nagoya-u.ac.jp
Not Recruiting
June. 21, 2021
July. 01, 2021
60
Interventional
single arm study
open(masking not used)
historical control
single assignment
treatment purpose
(1) Age
Age at the time of diagnosis (date of examination for histological diagnosis) is between 180 days and 18 years and 0 days of age.
(2) Histological diagnosis
Histopathologically confirmed as neuroblastoma or ganglioblastoma by open biopsy of the primary or metastatic lesion or bone marrow findings. However, cases in which urinary VMA/HVA is high and tumor cells are found in the bone marrow can be registered without pathological diagnosis of the primary tumor.
(3) Stage, prognostic factors and risk classification
A group classified as high risk in the INRG risk classification. At the time of incorporation, the following conditions are met;
-INRG L1 and L2 with confirmed MYCN amplification.
-In the case of INRG MS or M less than 18 months (less than 547 days), samples were submitted to measure MYCN amplification.
-INRG M for 18 months (547 days) or older
(4) Newly diagnosed untreated cases. However, one course of chemotherapy is acceptable for patients with INRG L1 and L2 disease.
(5) Organ damage.
No serious organ damage that would interfere with the protocol treatment in this study.
1. Performance status (PS): Karnofsky scale of 30 or more (16 years of age or older), or Lansky scale of 30 or more (15 years of age or younger)
2. Hematopoietic function: white blood cell count more than or equal to 2,000 /mm3
3. Liver function: ALT less than or equal to 300 IU/L and T.Bil less than or equal to 2.0 mg/dl. However, if T.Bil is judged to be elevated due to constitutional jaundice, this restriction is not applied.
4. Renal function: serum creatinine below the following age-specific serum creatinine reference values:
-Under 5 years of age: 0.8 mg/dL
-Between 5 and 10 years old: 1.2 mg/dL
-10 years old and under 18 years old: 1.5 mg/dL
5. Cardiac function: no cardiac disease requiring treatment.
(6) Infectious diseases
No active infection.
(7) Written consent.
Written consent to participate in the study has been obtained from the research subjects themselves and their proxies or proxies. Efforts will also be made to explain to the research subjects themselves according to their level of understanding to obtain assent.
(1) When the following 1) and 2) are found for the stage, prognostic factors and risk classification
1) No amplification of the MYCN gene in INRG stage M less than 18 months (less than 547 days) at diagnosis
2) Stage MS at diagnosis revealed no MYCN gene amplification and no 11q deletion
(2) Active multiple primary cancers (concurrent multiple primary cancers and metachronous multiple primary cancers with a disease free period of 5 years or less).
(3) Women who are pregnant, may be pregnant, or are breastfeeding.
(4) Women with comorbid psychosis or psychiatric symptoms who are considered to be unable to participate in the study.
(5) Has any other comorbidities that are not expected to be tolerated by the study protocol treatment.
(6) MIBG negative tumor
0age 6month 0week old over
18age old not
Both
Neuroblastoma
The patients receive three courses of chemotherapy consisting of cyclophosphamide, vincristine, pirarubicin, and cisplatin and the two courses of chemotherapy consisting of ifosfamide, carboplatin and etoposide.
Surgery, if possible, is performed between chemotherapies. Patients in the standard group will receive two courses of chemotherapy consisting of topotecan and cyclophosphamide and four courses of chemotherapy consisting of temozolomide and irinotecan followed by autologous hematopoietic stem cell transplantation with busulfan and melphalan as pretreatment. Patients in the poor prognosis group will receive two courses of chemotherapy consisting of topotecan and cyclophosphamide and four courses of chemotherapy consisting of temozolomide and irinotecan followed by autologous hematopoietic stem cell transplantation with busulfan and melphalan as pretreatment, then followed by KIR-ligand mismatched cord blood transplantation with reduced intensity conditioning with fludarabine, melphalan and TBI 2Gy after autologous hematopoietic stem cell transplantation if the patients meet eligibility criteria. Methotrexate and tacrolimus are used for GVHD prophylaxis; If no GVHD is seen, tacrolimus should be aggressively reduced and the goal is to discontinue it up to 3 months after transplantation. Local radiation therapy (19.8-30.6 Gy) is given after transplantation.
neuroblatoma
D009447
3-year progression-free survival rate
1. Overall survival time
2. Progression-free survival
3. Time to engraftment
4. Cumulative incidence of relapse
5. Type of progression (time to progression, location of progression)
6. 3-year progression-free survival rate after transplantation
7. Adverse events (including GVHD and infections)
Japan Agency for Medical Research and Development
Delegation Accounting Fund of Department of Pediatrics, Nagoya University Graduate School of Medicine
National Hospital Organization Review Board for Clinical Trials (Nagoya)
