A multicenter study of apheresis collection of peripheral blood mononuclear cells (PBMC) in patients with CD19 expressing malignancies who could be eligible for a CTL019 clinical research trial

1. Signed written informed consent, or signed parental permission form and assent form (as
applicable), must be obtained prior to any study procedures
2. Males and females * 18 years of age at the time of initial diagnosis and weighing * 40 kg
who are eligible to undergo a PBMC collection by apheresis for potential future CTL019
manufacturing for use in a CTL019 trial
3. CD19 expressing malignancy for which a CTL019 treatment protocol is currently
enrolling or under IRB/EC review
4. Hemoglobin level * 9.0 g/dL at screening. Transfusion support can be provided within 24
hours of starting the apheresis procedure to meet this criterion
5. Platelet count * 50,000/microliter at screening. Transfusion support can be provided
within 24 hours of starting the apheresis procedure to meet this criterion
6. Prothrombin Time (PT)/ Partial Thromboplastin Time (PTT) * 1.5 x ULN at screening.
Transfusion support can be provided within 24 hours of starting the apheresis procedure to
meet this criterion
7. Peripheral blood absolute lymphocyte count (ALC) * 500/microliter at screening
or if ALC <500/uL, then the absolute CD3 lymphocyte count must be *150/uL at
screening
8. For patients who have undergone allogeneic transplant, must be * 3 months from
allogeneic SCT at the time of apheresis

1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female
after conception and until the termination of gestation, confirmed by a positive hCG
laboratory test at screening
3. Human Immunodeficiency Virus (HIV) infection at screening
5. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) at
screening
6. Any patient that in the opinion of the investigator is not medically stable to undergo the
apheresis procedure or will not comply with the visit schedules or procedures
7. Treatment with any prior gene therapy product
8. Patient has participated in a research study using an investigational agent within the last
30 days prior to screening
9. Patient should not have received long-acting growth
factors or drugs used for cell mobilization (e.g. Neulastsa/pegflilgrastim) within 14 days
of the eukapheresis procedure. Use of short-acting growth factors of drugs
used for cell mobilization (e.g. G-CSF/Neupogen/filgrastim, plerixafor) must be * 5 days leukapheresis procedure
11. The following treatments/medications are excluded:
**Chemotherapy:
**-Cytotoxic chemotherapy drugs must not be given within 2 weeks of apheresis
- Intrathecal chemotherapy (IT): Recommend holding IT prior to leukapheresis
collection. If clinically indicated, IT Ara-C may be given and leukapheresis
collection started any time following IT Ara-C. Leukapheresis collection may
be started * 7 days after IT methotrexate (MTX)
**- Pegylated-asparaginase must be stopped >4 weeks prior to apheresis
**Low dose daily or weekly maintenance chemotherapy should be stopped * 2
weeks prior to apheresis
- Clofarabine may be associated with prolonged lymphopenia. This should be
taken into consideration when evaluation the optimal timing for
leukapheresis collection. An interval of * 8 weeks from the
patient*s last clofarabine treatment is recommended
-Short-acting drugs(e.g tyrosine kinase inhibitors, ibrutinib and
hydroxyurea) must not be given within a 72 hour window of the
leukapheresis procedure
**Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to apheresis.
However, the following physiological replacement doses of steroids are allowed: * 12
mg/m2/day hydrocortisone or equivalent
**Immunomodulatory drugs (e.g. IFN-gamma, anti-TNF-alpha): should be stopped
* 2 weeks prior to apheresis
**Allogeneic cellular therapy:
- Must be * 3 months from allogeneic stem cell transplant at the time of
leukapheresis.
- Must not have presence of grade 2 to 4 acute graft-versus-host disease (GVHD)
or extensive chronic GVHD.
- Any donor lymphocyte infusions (DLI) must be
completed > 4 weeks prior to apheresis
**GVHD therapies: Any drug used to prevent or treat GVHD must be stopped > 2
weeks prior to apheresis (e.g. calcineurin inhibitors, methotrexate or other
chemotherapy drugs, mycophenolate, rapamycin, thalidomide, or immunosuppressive
antibodies such as anti-TNF-*, anti-IL6 or anti-IL6R). Topical steroids for localized
treatment of GVHD are allowed
- Anti T-cell Directed Therapy: Administration of any T cell lytic or toxic agent (e.g.
alemtuzumab) is strongly discouraged since residual lytic levels may destroy T-cells
in the leukapheresis collection and/or prevent their in vitro CTL019
manufacturing.
- Anti-CD19 directed therapy Has had treatment with any prior anti-CD19/anti-CD3
therapy, or any other anti-CD19 therapy unless a specific Novartis CTL019 treatment
protocol would allow for prior anti-CD19 directed therapy
12. Hepatitis B (see Appendix 1 for interpretation of Hepatitis B results) or active hepatitis C
(HCV RNA positive)
13. Patients with an acute infection (bacterial, viral or fungal) or a positive blood culture
should not undergo leukapheresis collection. A full course of anti-infective therapy must
be administered before leukapheresis collection can occur to avoid contamination of the
product.*