Leukapheresis for CAR-Therapy Manufacturing

Background:

- Leukapheresis is a necessary step to developing a CAR therapy cellular product. There
are numerous clinical trials underway in the NCI utilizing CAR therapy.

- The purpose of this protocol is to develop a streamlined process whereby patients
undergo apheresis for development of a CAR cell product on a subsequent therapeutic
clinical trial, which can be administered when the patient needs investigational
therapies.

- Allowing for collection of the leukapheresis product in a protocol separate from the
therapeutic protocol would allow for the best optimization of:

- Patient care and disease burden

- Timing and coordination of cell infusion

- Collection in patients with high-risk disease who have no current detectable
disease but have a very high likelihood of relapse.

Objective:

To obtain via the leukapheresis process by which cells will be collected and stored for use
in CCR CAR therapy clinical trials.

Eligibility:

-Patients 3-30 years of age, at least 15 kg, with relapsed/refractory leukemia or lymphoma
that has recurred after or not responded to one or more standard regimens and/or deemed
incurable by standard therapy and who meet all eligibility criteria are eligible to
participate.

Design:

- Once a patient is determined to be a potential candidate for one of the NCI CAR clinical
trials, they will undergo leukapheresis, as estimated by recipient weight and target
cell harvest dose in the Department of Transfusion Medicine (DTM).

- No treatments, investigational or standard therapy will be administered on this
protocol.

- Up to 24 patients per year may be enrolled on this study. In planning for future CAR
therapy trials, we expect this study to remain open for up to 5 years for a total of 120
patients to be enrolled.

- INCLUSION CRITERIA:

- Age: greater than or equal to 3 and less than or equal to 30 years

- Weight greater than or equal to 15 kg

- Confirmation of leukemia or lymphoma diagnosis provided by prior flow cytometry, PCR
or H&E verification.

- Disease Status:

- Relapsed/refractory leukemia or lymphoma that has failed one standard and one
salvage therapy and are not in remission at the time of leukapheresis, OR

- Previously treated patients without detectable disease at the time of
leukapheresis but at high-relapse risk.

- Potentially eligible for future NIH-CAR therapy based on the following:

- Adequate performance status: Patients > 10 years of age: Karnofsky greater than
or equal to 50%; Patients less than or equal to 10 years of age: Lansky scale
greater than or equal to 50%

- Adequate organ function:

- absolute neutrophil count >750/mcL*

- platelets greater than or equal to 30,000/mcL*

- total bilirubin less than or equal to 2 X ULN (except in the case of subjects
with documented Gilbert s disease > 3x ULN)

AST(SGOT)/ALT(SGPT) less than or equal to 20 X institutional upper limit of normal for age
and laboratory normal ranges

creatinine within age adjusted normal institutional limits (see table below)

OR

creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with
creatinine levels above institutional normal.

- Age less than or equal to 5 years- Maximun serum creatinine of 0.8

- Age less than or equal to 10 and greater than 5 years- Maximun serum creatinine of 1.0

- Age greater than 10 years- Maximun serum creatinine of 0.8

- Cytopenias deemed to be disease-related and not therapy-related are exempt from
this exclusion.

- Patients, parents/guardian(s), legally authorized representative (LAR), or
durable power of attorney must be able to give consent and sign the informed
consent document.

EXCLUSION CRITERIA:

- Transfusion refractory thrombocytopenia such that platelet count cannot be adequately
supported with transfusions to be maintained greater than or equal to 30,000/mcL

- Active DIC, bleeding or coagulopathy which cannot be corrected with minimal
intervention

- Rapidly progressive disease or hyperleukocytosis greater than or equal to 50,000
blasts/mcL

- Symptomatic, uncontrolled or severe intercurrent illness that would compromise the
ability to tolerate CAR therapy based toxicity

- Systemic chemotherapy less than or equal to 2 weeks (6 weeks for clofarabine or
nitrosoureas) or radiation therapy less than or equal to 3 weeks prior to
leukapheresis; with the following exception

--Maintenance chemotherapy including tyrosine kinase inhibitors will be allowed up to
one week prior to apheresis (there will be no wash-out required for steroids).

- Other anti-neoplastic investigational agents, or antibody-based therapies currently or
within 2 weeks prior to leukapheresis (i.e. start of protocol therapy);

- Subjects must have recovered from the acute side effects of their prior therapy, such
that eligibility criteria are met. Cytopenias deemed to be disease-related and not
therapyrelated are exempt from this exclusion.

- 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

- Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at
screening

- Human Immunodeficiency Virus (HIV) infection at screening (The experimental treatments
being evaluated depend upon an intact immune system. Patients who are HIV seropositive
can have decreased immune competence and thus be less responsive to the experimental
treatment and more susceptible to its toxicities)

- Any patient that in the opinion of the investigator is not medically stable to undergo
the leukapheresis procedure or will not comply with the visit schedules or procedures