臨床研究等提出・公開システム

国立研究開発法人国立がん研究センター中央病院

National Cancer Center Hospital

京都大学医学部附属病院

Kyoto University Hospital

非無作為化比較、非盲検、非対照、譚群比較、治療

Non-randomized, open-label, uncontrolled, single-arm, treatment

主な選択基準
・文書による同意が得られた患者
・再発又は難治性小児B細胞性ALL（化学療法が奏効しない、同種幹細胞移植(SCT)後に再発した、又は他の理由で同種SCTが適さない患者）
・再発した患者の場合，本試験登録前3ヵ月以内にフローサイトメトリーで骨髄又は末梢血にCD19腫瘍の発現が確認されている
・スクリーニング時の形態的評価で骨髄のリンパ芽球が5%以上
・余命が12週を超える
・3歳以上（スクリーニング時），21歳以下（最初の診断時）
・スクリーニング時の患者状態（PS）がKarnofskyスコア（16歳以上の場合）又はランスキースコア（15歳以下の場合）で50以上

1. Relapsed or refractory pediatric B-cell ALL
2. Adequate organ function
3. For relapsed patients, documentation of CD19 tumor expression within 3 months of study entry.
4. Bone marrow with >= 5% lymphoblasts by morphologic assessment at screening.
5. Life expectancy > 12 weeks.
6. Karnofsky (age >=16 years) or Lansky (age < 16 years) performance status >= 50 at screening
7. Signed written informed consent and assent forms
8. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, store leukapheresis product
9. Must have an apheresis product of non-mobilized cells received and accepted by the manufacturing site.
10. Cohort 1 only:
1. First relapse AND hypodiploid cytogenetics OR
2. First relapse AND t(17;19) with defined TCF3-HLF fusion OR
3. First relapse with any cytogenetics provided the relapse occurred =< 36 months of initial diagnosis AND MRD at end of reinduction therapy is >=0.01% by flow cytometry (local assessment)

主な除外基準
・髄外単独病変の再発
・遺伝性の症候群の併存
・バーキットリンパ腫／白血病
・悪性疾患の既往
・遺伝子療法の治療歴
・抗CD19／抗CD3療法，又は，その他の抗CD19療法の治療歴
・活動性若しくは潜在性B型肝炎，活動性C型肝炎，又はコントロール不良の感染症
・ヒト免疫ウイルス（HIV）が陽性の場合
・グレード 2～4の急性又は広汎性の慢性移植片対宿主病（GVHD）
・活動性の中枢神経系（CNS）悪性疾患

1. Isolated extra-medullary disease relapse
2. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
5. Treatment with any prior gene therapy product
6. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
8. Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
9. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).
10. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.
11. Patient has an investigational medicinal product within the last 30 days prior to screening.
12. Pregnant or nursing (lactating) women.
13. Women of child-bearing potential, defined as physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception for at least 12 months after the CTL019 infusion and after CAR T-cells are no longer present by qPCR on two consecutive tests
14. Sexually active males must use a condom during intercourse at least 12 months after the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive tests

3歳以上

3age old over

21歳以下

21age old under

男性・女性

Both

試験完了

completed