A study to assess the safety, feasibility and clinical activity of JCAR015, a CAR-T cell therapy, in adults with B-cell acute lymphoblastic leukemia
- Conditions
- B-cell Acute Lymphoblastic Leukemia (ALL)MedDRA version: 19.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2016-001706-42-ES
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 105
Part A
Inclusion Criteria common to all cohorts:
1. Age =18 years at the time of signing the informed consent form
2. Subject must understand and voluntarily sign an ICF prior to any
study-related assessments/procedures being conducted
3. Subject is willing and able to adhere to the study visit schedule and
other protocol requirements
4. Diagnosis of B-cell ALL
5. Evidence of CD19 expression via flow cytometry (peripheral blood or
bone marrow) or immunohistochemistry (bone marrow biopsy)
6. Eastern Cooperative Oncology Group (ECOG) performance status = 2
7. No contraindications to cyclophosphamide. This includes subjects
with:
· hypersensitivity to cyclophosphamide, any of its metabolites
· acute infections
· bone marrow aplasia or bone marrow depression prior to treatment
· urinary tract infection
· acute urothelial toxicity from cytotoxic chemotherapy or radiation
therapy
· urinary outflow obstruction
· obstruction
8. Adequate organ function, defined as:
a. Serum creatinine = 1.5 × age-adjusted upper limit of normal (ULN) OR
calculated creatinine clearance (Cockcroft and Gault, see Appendix D) >
30 mL/min/1.73 m2
b. Alanine aminotransferase (ALT) = 5 × ULN and direct bilirubin < 2.0
mg/dL (or < 3.0 mg/dL for subjects with leukemic infiltration of the
liver)
c. Adequate pulmonary function, defined as = Grade 1 dyspnea and
oxygen saturation (SaO2) = 92% on room air
d. Adequate cardiac function, defined as left ventricular ejection fraction
(LVEF) = 40% as assessed by echocardiogram (ECHO) or multiple
uptake gated acquisition (MUGA) performed within 1 month of signing
the informed consent form
9. Adequate central or peripheral vascular access for leukapheresis
procedure. For subjects requiring central venous catheter (CVC)
placement, a surgical consultation indicating subject eligibility for CVC
placement is sufficient for enrolment.
10. Subjects must agree to not donate blood, organs, sperm or semen,
and egg cells for usage in other individuals without recipient knowledge
about exposure to a genetically modified organ by the donor and having
been informed about the potential risks associated with it at any point
after receiving JCAR015 infusion.
11. Females of childbearing potential (FCBP) must:
a. Have two negative pregnancy tests as verified by the Investigator
(one negative serum beta human chorionic gonadotropin (ß-hCG)
pregnancy test result within 7 days prior to the first dose of
cytoreductive chemotherapy, and one negative serum or urine
pregnancy test at the Part B screening evaluation prior to first JCAR015
infusion). She must agree to have another pregnancy test 90 days post
final JCAR015 dose. This applies even if the subjec
Part A
1. Isolated extramedullary disease relapse
2. Concomitant genetic syndrome such as Fanconi anemia, Kostmann
syndrome, Shwachman syndrome, or any other known bone marrow
failure syndrome
3. Burkitt's lymphoma/leukemia or chronic myelogenous leukemia (CML)
lymphoid blast crisis (p210 BCR-ABL+)
4. Prior malignancy, unless treated with curative intent and with no
evidence of active disease present for > 5 years before signing the
informed consent form, with the following exceptions:
a. Subjects with Stage I breast cancer that has been completely and
successfully treated, requiring no therapy or only anti-hormonal therapy
b. Subjects with T1N0M0 or T2N0M0 colorectal cancer who have been
completely and successfully resected and who are disease-free for > 2
years prior to screening
c. Subjects with indolent prostate cancer, defined as clinical stage T1 or
T2a, Gleason score = 6, and prostate-specific antigen (PSA) < 10 ng/mL,
requiring no therapy or only anti- hormonal therapy
d. Subjects with a history of basal cell or squamous cell carcinoma of the
skin, or carcinoma in situ of the cervix, fully resected, and with no
evidence of active disease
5. Treatment with any prior gene therapy product
6. Active hepatitis B, active hepatitis C, or any human immunodeficiency
virus (HIV) infection at the time of signing the informed consent form
7. Systemic fungal, bacterial, viral, or other infection that is not
controlled (defined as exhibiting ongoing signs/symptoms related to the
infection and without improvement, despite appropriate antibiotics or
other treatment) at the time of signing the informed consent form
8. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or
extensive chronic GVHD at the time of signing the informed consent form
9. Active CNS involvement by malignancy, defined as CNS-3 per NCCN
guidelines. Subjects with a history of CNS disease that has been
effectively treated (defined as one documented negative CSF evaluation
within 1 month prior to signing the informed consent form) will be
eligible
10. History of any one of the following cardiovascular conditions within
the past 6 months of signing the informed consent form: Class III or IV
heart failure as defined by the New York Heart Association (NYHA),
cardiac angioplasty or stenting, myocardial infarction, unstable angina,
or other clinically significant cardiac disease
11. History or presence of clinically relevant CNS pathology such as
epilepsy, generalized seizure disorder, paresis, aphasia, stroke, severe
brain injuries, dementia, Parkinson's disease, cerebellar disease, organic
brain syndrome, or psychosis
12. Participation in an investigational research study using an
investigational agent within 30 days of signing the informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method