kurzprotokoll cctl019b2202

KURZPROTOKOLL
CCTL019B2202
Öffentlicher Titel
Phase II Studie zu CTL019 bei paediatrischen Patienten mit rezidiviert/refraktärer akuter
B-ALL
Wissenschaftl. Titel
A Phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in
pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia
Kurztitel
CCTL019B2202
Studienart
multizentrisch, prospektiv, Therapiestudie, offen/unverblindet, einarmig
Studienphase
Phase II
Erkrankung
HAEMA: ALL: Rezidiviert/refraktär
PAED: Leukämien & Lymphome: Rezidiviert/refraktär
Ziele
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Evaluate the efficacy of CTL019 therapy as measured by overall remission rate
(ORR) during the 6 months after CTL019 administration, which includes CR and CR
with incomplete blood count recovery (CRi) as determined by IRC assessment
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Evaluate the percentage of patients who achieve a best overall response (BOR) of
CR or CRi with a MRD negative bone marrow by central analysis using qPCR
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Evaluate the percentage of patients who achieve CR or CRi at Month 6 without SCT
between CTL019 infusion and Month 6 response assessment
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Evaluate the percentage of patients who achieve CR or CRi and then proceed to
SCT while in remission before Month 6 response assessment
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Evaluate the duration of remission (DOR)
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Evaluate the relapse-free survival (RFS)
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Evaluate the event-free survival (EFS)
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Evaluate the overall survival (OS)
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Evaluate the safety of CTL019 therapy
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Characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence,
trafficking) of CTL019 cells
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Describe the prevalence and incidence of immunogenicity to CTL019
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Relapsed or refractory pediatric B-cell ALL.
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a.2nd or greater Bone Marrow (BM) relapse OR.
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b.Any BM relapse after allogeneic stem cell transplantation (SCT) and must be 6
months from SCT at the time of CTL019 infusion OR
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c. Primary refractory as defined by not achieving a CR after 2 cycles of a standard
chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1
cycle of standard chemotherapy for relapsed leukemia OR
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d.Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI
therapy is contraindicated OR.
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e.Ineligible for allogeneic SCT.
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.For relapsed patients, documentation of CD19 tumor expression in bone marrow or
peripheral blood by flow cytometry within 3 months of study entry.
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Adequate organ function defined as:
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a.Renal function defined as: A serum creatinine based on age/gender as follows:
Maximum Serum Creatinine (mg/dL) - Age/Male/Female: 1 to < 2 years/0.6/0.6; 2 to
< 6 years/0.8/0.8; 6 to < 10 years/1.0/1.0; 10 to < 13 years/1.2/1.2; 13 to < 16
years/1.5/ 1.4; 16 years/1.7/1.4.
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b.Alanine Aminotransferase (ALT) 5 times the upper limit of normal (ULN) for age.
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c.Bilirubin < 2.0 mg/dL.
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d.Grade1 dyspnea and pulse oxygenation > 91% on room air.
Einschlusskriterien
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KURZPROTOKOLL
CCTL019B2202
Ausschlusskriterien
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e.Left Ventricular Shortening Fraction (LVSF) 28% confirmed by echocardiogram
(ECHO), or Left Ventricular Ejection Fraction (LVEF) 45% confirmed by
echocardiogram or Multiple Uptake Gated Acquisition (MUGA).
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Bone marrow with 5% lymphoblasts by morphologic assessment at screening.
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Life expectancy > 12 weeks.
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Age 3 at the time of screening to age 21 at the time of initial diagnosis
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Karnofsky (age 16 years) or Lansky (age < 16 years) performance status 50 at
screening.
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Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.
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Other protocol defined inclusion criteria may apply.
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Isolated extra-medullary disease relapse
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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.
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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)
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Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
intent and with no evidence of active disease
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Treatment with any prior gene therapy product
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Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
therapy
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Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or
any uncontrolled infection at screening
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Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
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Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease
(GVHD)
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Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines.
Note: Patients with history of CNS disease that has been effectively treated will be
eligible
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Patient has an investigational medicinal product within the last 30 days prior to
screening
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Pregnant or nursing (lactating) women. NOTE: female study participants of
reproductive potential must have a negative serum or urine pregnancy test performed
within 48 hours before infusion
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Women of child-bearing potential (defined as all women physiologically capable of
becoming pregnant) and all male participants, unless they are using highly effective
methods of contraception for a period of 1 year after the CTL019 infusion. Highly
effective contraception methods include:
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a.Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are NOT acceptable methods of contraception
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b.Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy) or tubal ligation at least six weeks before taking study treatment. In
case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment
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c.Male sterilization (at least 6 months prior to screening). For female patients on the
study the vasectomized male partner should be the sole partner for that patient.
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KURZPROTOKOLL
CCTL019B2202
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d. BOTH of the following forms of contraception must be utilized: - Use of oral,
injected or implanted hormonal methods of contraception or other forms of hormonal
contraception that have comparable efficacy (failure rate <1%), for example hormone
vaginal ring or transdermal hormone contraception. - Barrier methods of
contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with
spermicidal foam/gel/film/cream/vaginal suppository
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e.Use of IUDs are excluded due to increased risks of infection and bleeding in this
population.
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f.In case of use of oral contraception, women must be stable on the same pill for a
minimum of 3 months before taking study treatment.
Alter
3-21
Status
Aktiv
Beginn der Rekrutierung
18.02.2016
Fallzahl
60
Prüfzentren
Universitätsklinikum Frankfurt
Klinik für Kinder- und Jugendmedizin
Theodor-Stern-Kai 7
60590 Frankfurt am Main
Gudrun Sach
Tel: 069 6301-83643
Fax: 069 6301-87735
Gudrun.sach@kgu.de
Sponsoren
Novartis Pharma
Förderer
Novartis Pharma
Registrierung in anderen
Studienregistern
EUDRACT 2013-003205-25
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Ohne Gewähr für Richtigkeit oder Vollständigkeit, www.uct-frankfurt.de
Stand: 15.01.2017; Seite 3 von 3