A clinical study to provide the opportunity to be treated with CTL019, an investigational gene therapy, for children and adolescent patients with a recurrent form of B-cell acute lymphoblastic leukaemia after the closure of the Novartis single-arm phase II pivotal registration trial (Study CCTL019B2202) and to collect additional safety information.

Phase 1

• Conditions: Paediatric/young adult patients with B-cell acute lymphoblastic leukaemia who are chemo-refractory, relapsed after allogeneic SCT, or are otherwise ineligible for allogeneic SCT.; MedDRA version: 19.1 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864; MedDRA version: 19.1 Level: LLT Classification code 10063621 Term: Acute lymphoblastic leukaemia recurrent System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001991-31-ES
• Lead Sponsor: ovartis Farmacéutica, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-13
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 55

Inclusion Criteria

Patients eligible for inclusion in this program have to meet all of the following criteria:
1. Relapsed or refractory B-cell ALL in pediatric or young adult patients:
a. Second or greater bone marrow relapse, OR
b. Any bone marrow relapse after allogeneic SCT and must be = 6 months from SCT at the time of CTL019 infusion, OR
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
d. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated, OR
e. Ineligible for allogeneic SCT because of:
- Comorbid disease,
- Other contraindications to allogeneic SCT conditioning regimen,
- Lack of suitable donor,
- Prior SCT,
- Declines allogeneic SCT as a therapeutic option after documented discussion about the role of SCT with a bone marrow transplantation physician not part of the program team.
2. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of program entry.
3. Adequate organ function defined as:
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.
b. Alanine Aminotransferase (ALT) = 5 times the upper limit of normal (ULN) for age.
c. Bilirubin < 2.0 mg/dL.
d. Must have a minimum level of pulmonary reserve defined as = Grade 1 dyspnea and pulse oxygenation > 91% on room air.
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) within 7 days of screening.
4. Bone marrow with = 5% lymphoblasts by morphologic assessment at screening.
5. Life expectancy > 12 weeks.
6. Age 3 years at the time of screening to age 21 years at the time of initial diagnosis.
7. Karnofsky (age = 16 years) or Lansky (age < 16 years) performance status = 50 at screening.
8. Signed written informed consent and assent forms if applicable must be obtained prior to
any program procedures.
9. Must meet the institutional criteria to undergo leukapheresis or have an acceptable, stored
leukapheresis product.
10. Once all other eligibility criteria are confirmed, must have a leukapheresis product of nonmobilized cells received and accepted by the manufacturing site. Note: Leukapheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other eligibility criteria is received.

Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? yes
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Exclusion Criteria

Exclusion Criteria:
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.
10. 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.
11. Patient has an investigational medicinal product within the last 30 days prior to screening.
12. 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.
13. 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:
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.
b. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least 6 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.
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.
d. 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.
e. Use of IUDs are excluded due to increased risks of infection and bleeding in this population. However, IUD inserted prior to consent may remain in place, and a second method of contraception is mandated.
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.

Wome

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified