CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)

Earlier, a healthy donor provided blood to make ANCHOR cells in the laboratory. These cells
were grown and frozen for later use. To make the ANCHOR cells, the investigators took the
donor blood and stimulated it with growth factors to make the NKT cells grow. To get the CD19
antibody, CD28 and IL-15 into the NKT cells, they were infected with a virus, called a
retrovirus. This virus cannot grow and infect other cells, but delivered a new genetic
message into the ANCHOR cells that provides the instructions for the cells to make the CD19
antibody, CD28 and IL-15. This new genetic message will also help the investigators to find
the ANCHOR cells in the blood after they are injected. Because patients will have received
cells with a new gene in them, patients will be followed for a total of 15 years to see if
there are any long term side effects of gene transfer.

Patients will be assigned a dose of ANCHOR cells. This is a dose escalation study. This means
that at the beginning, patients will be started on the lowest dose of ANCHOR cells. Once that
dose schedule proves safe, the next group of patients will be started at a higher dose. This
process will continue until all 4 dose levels are studied. If the side effects are too
severe, the dose will be lowered or the infusions will be stopped.

In this study, patients will receive treatment with cyclophosphamide and fludarabine. These
drugs will decrease the numbers of the patients own immune cells before the ANCHOR cells are
infused.

The patient will be given an injection of ANCHOR cells into the vein through an IV at the
assigned dose. Before receiving the injection, the patient may be given a dose of Benadryl
and Tylenol. The injection will take about 20 minutes. The patient will then be monitored in
the clinic for up to 2 hours. Patients will need to stay in Houston for 4 weeks after the
ANCHOR cell infusion to monitor them for side effects. Patients will have follow-up visits
(at weeks 1, 2, 3, 4, and 6; months 3, 6, 9, and 12; twice a year for 4 years and then once a
year for the next 10 years - for a total of 15 years) and scheduled disease evaluations after
the ANCHOR cell infusion (at week 4 and then as clinically needed).

The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist
Hospital.

Medical tests before treatment--

Before being treated, the patient will receive a series of standard medical tests:

- Physical exam and History

- Blood tests to measure blood cells, kidney and liver function

- Measurements of tumor by scans and/or bone marrow studies

- A urine pregnancy test, when applicable

Medical tests during and after treatment--

Patients will receive standard medical tests when getting the infusions and afterwards. The
evaluations that will be done at these visits include:

- Physical exams and History

- Blood tests to measure blood cells, kidney and liver function

- Measurements of the tumor by scans and/or bone marrow studies 4 weeks after the infusion

To learn more about the way the ANCHOR cells are working and how long they last in the body,
extra blood will be drawn. On the day patients receive the cells, blood will be taken before
the cells are given and a few hours afterwards. Other blood will be drawn one week after the
infusion, 2 weeks, 3 weeks (optional), 4 weeks, and 6 weeks after the infusion, at 3 months,
at 6 months, at 9 months, at 1 year, twice a year for 4 years, then yearly for the next 10
years - for a total of 15 years.

During the time points listed above, if the ANCHOR cells are found in the patient's blood
above a certain amount, an extra 5 mL of blood may need to be collected for additional
testing.

If the patient has a biopsy of a lymph node, like a repeat tumor or bone marrow study, the
investigators may ask to have a piece for research purposes.

Patients will receive supportive care for any acute or chronic toxicities, including blood
components or antibiotics, and other intervention as appropriate.

Treatment Inclusion Criteria:

1. Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).

2. The disease is:

1. Relapsed or refractory after two or more lines of therapy, including a CD20
antibody, if an indolent lymphoma or CLL.

2. Relapsed or refractory after two or more lines of therapy, including a CD20
antibody and an anthracycline, and the patient is ineligible for autologous stem
cell transplantation, if an aggressive or highly aggressive lymphoma.

3. Relapsed or refractory after two or more lines of therapy, if ALL.

3. Measurable disease by current criteria.

4. Age >17 and ≤75 years.

5. Bilirubin less than 3 times the upper limit of normal.

6. AST less than 5 times the upper limit of normal.

7. Estimated GFR ≥ 50 mL/min.

8. Pulse oximetry of ≥ 90% on room air

9. Karnofsky or Lansky score of ≥ 70%.

10. Recovered from the acute toxic effects of all prior chemotherapy based on the
enrolling physician's assessment (if some effects of chemotherapy are expected to last
long term, patient is eligible if meeting other eligibility criteria).

11. Life expectancy of greater than 12 weeks.

12. Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after the study is concluded. The
male partner should use a condom.

13. Patients must sign an informed consent indicating that they are aware this is a
research study and have been told of its possible benefits and toxic side effects.
Patients or their guardians will be given a copy of the consent form.

Treatment Exclusion Criteria:

1. Currently receiving any investigational agents or received any cellular therapies
within the previous 6 weeks.

2. History of hypersensitivity reactions to murine protein-containing products.

3. Pregnant or lactating.

4. Active infection with HIV or HTLV.