A Phase I Clinical Trial of CART cell therapy for refractory/ relapsed acute lymphoblastic leukemia with unmet needs in children, adolescents and young adults: feasibility and safety study (REALL_CART)

Prior treatment

• Enrolled in another clinical trial in the previous 4 weeks.
• Active immunosuppressive therapy with the exception of prednisone 10 mg/day (or equivalent), within 7 days prior to enrolment.
• Sexually active patients must be willing to utilize one of the more effective birth control methods for at least 12 months after the infusion and until CAR-T cells are no longer present on two consecutive tests. Male partner should use a condom. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant. Highly effective contraception methods include, as defined by the CTFG recommendations (available at h t t p s : / / w w w . h m a . e u / f i l e a d m i n / d a t e i e n / H u m a n _ M e d i c i n e s / 0 1 -About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf): o Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) o Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) o Intrauterine device (IUD) o Intrauterine hormone-releasing system o Bilateral tubal occlusion o Vasectomized partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success) o Sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject). Sexually active males should use a condom during intercourse for at least 12 months after the infusion and until CAR-T cells are no longer present on two consecutive tests.

Other illness

• Active infection requiring systemic medical therapy including clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, adenovirus, BK-virus, HHV-6 or Aspergillus.
• Presence of CNS-3 disease or uncontrolled seizure disorder.
• Any other condition that, in the opinion of the PI, may interfere with the efficacy and/or safety evaluation of the trial.

Lab values

• Any of the following cardiac criteria: cardiac echocardiography with LVSF<30% or LVEF<40%; or clinically significant pericardial effusion.
• GFR <30 ml/min or bilirubin >3 times the upper limit of normality (unless due to Gilbert's syndrome).

Other

• Pregnant or lactating women.

• Age: Patients <30 years at diagnosis and/or relapse.
• Lansky (age <16 years) or Karnofsky (age ≥16 years) score of 50 or greater.
• Life expectancy greater than 12 weeks.
• Absolute neutrophil count (ANC) ≥ 500/μL unless, in the opinion of the investigator, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy.
• Platelet count ≥ 50,000/μL unless, in the opinion of the investigator, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy.
• Absolute lymphocyte count ≥ 100/μL.
• Adequate renal, hepatic, pulmonary, and cardiac function.
• Adequate venous access and absence of contraindications for lymphoapheresis.
• Patients with a seizure disorder may be enrolled if well controlled with anticonvulsants.
• Patient or patient's legal representative, parent(s), or guardian able to provide written informed consent.
• Diagnosis: o ARM A: CD19+/- CD22+ B-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available. Treatment with previous CART CD19 therapy is permitted, but is not mandatory. / o ARM B: T-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available.
• Patients diagnosed with ALL must be suitable for allogeneic HSCT and willing to proceed to transplant if the CART treatment induces complete remission and the investigator believes it is the best option.
• For ARM B there must be a suitable haploidentical donor (following local SOP).