Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL

The patient will give blood to make TAA-specific cytotoxic T cells in the lab. These cells
will be grown and frozen. If the TAA-specific cytotoxic T cells can be made, the time from
collection of the blood to manufacture of T cells for administration to the patient is about
1 to 2 months.

There are 4 stages of this study: an antigen-escalation phase, a dose-escalation stage, aza
stage and pediatric patients stage.

The antigen-escalation phase will be first. Patients will receive TAA-specific T cells
targeting first 1 and then 2 TAAs. Once this schedule proves safe, the next group of patients
will receive TAA-specific T cells targeting first 2 and then 3 TAAs. This process will
continue until all 4 levels are studied. This means that the final cohort of patients will
receive TAA-specific T cells targeting first 4 and then 5 TAAs. If the side-effects are too
severe, the number of TAAs being targeted will be lowered or the T cell injections will be
stopped. Each patient will receive 2 infusions at the same dose 28 days apart

After the antigen-escalation phase, the dose-escalation phase will begin. Patients will be
started on the lowest dose (1 of 3 different levels) of T 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 3 dose levels are studied. If the side-effects are too severe, the dose
will be lowered or the T cell injections will be stopped. Each patient will receive 2
infusions at the same dose 14 days apart

After the dose escalation stage, adult patients will be enrolled on the aza stage where they
will receive the drug aza followed by two infusions of T cells on dose level 2. Patients will
be given 3 cycles of aza (administered daily through a vein for 5 days, every 28 days)
followed by 2 doses of multiTAA-specific T cells administered 14 days apart. Before the
patient is given the aza they will be given a drug to help prevent nausea and vomiting.

On the pediatric stage, pediatric patients will receive 2 infusions of T cells on dose level
2. The T cells will be given 14 days apart.

The cells will be injected by IV over 10 minutes. The patients may be pre-treated with
acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and
diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the T cell
administration. If after the second infusion there is a reduction in the size of the
patient's lymphoma on CT or MRI scan as assessed by a radiologist, the patient can receive up
to six (6) additional doses of the T cells at monthly intervals if they wish. All of the
treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist
Hospital or Texas Children's Hospital.

In between the first and second T cell infusions and for 6 weeks after the last infusion, the
patient should not receive any other anti-cancer treatments such as radiation therapy or
chemotherapy. If the patient does receive any other therapies in-between the first and second
infusion of T cells, they will be taken off treatment and will not be able to receive the
second infusion of T cells.

MEDICAL TESTS BEFORE TREATMENT

- Physical exam.

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

- Measurements of your tumor by routine imaging studies. We will use the imaging study
that was used before to follow your tumor: CT, MRI, or PET.

- Pregnancy test if you are a female who can have children.

MEDICAL TESTS AFTER TREATMENT

- Imaging study 6 weeks after the 2nd TAA-CTL infusion.

To learn more about the way the T cells are working in the patient's body, an extra 20-40 mL
(4-8 teaspoons) of blood will be taken before each cycle of aza (if applicable), 2 weeks
after each cycle of aza (if applicable), before each T-cell infusion, and at Weeks 1, 2, 4
and 6. One additional blood sample might be drawn 3 to 4 days post the T-cell infusion; this
is optional. Afterwards, blood will be collected at 3, 6, 9 and 12 months after the last
infusion. The blood may be drawn from a central line at the time of the patient's regular
blood tests. Investigators will use this blood to see how long the T cells last,and to look
at the immune response to the patient's cancer.

Study Duration: Patients will be on active study participation for approximately one year.
Patients who receive additional doses of the T cells as described above will be actively
followed until 1 year after their last dose of T cells. Investigators will then remain in
contact with patients once a year for up to 4 additional years (total of 5 years follow-up)
in order to evaluate disease response long-term.

Inclusion Criteria:

PROCUREMENT:

1. Any patient regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin lymphoma.

2. Life expectancy of 6 weeks or greater.

3. Hgb greater than or equal to 7.0

4. Patient and,or parent,guardian able to give informed consent.

TREATMENT:

1. Any patient regardless of sex, with a diagnosis of Hodgkin or non-Hodgkin lymphoma:

Group A: Patients greater than or equal to 18 years old

- with active disease:

- in second or subsequent relapse.

- in first relapse for indolent lymphoma after first-line therapy for relapse.

- or first relapse if immunosuppressive chemotherapy contraindicated.

- primary refractory disease or if persistent disease after first-line therapy
of relapse.

- or multiply relapsed patients in remission who are at a high risk of relapse.

- or the lymphoma is a second malignancy e.g. a Richters transformation of CLL
after failing front line therapy.

OR

Group B: Patients greater than or equal to 18 years old after autologous or syngeneic
SCT (as adjuvant therapy).

OR

Group C: azacytidine plus multiTAA-T cells Patients greater than or equal to 18 years
old

- with active disease in:

- second or subsequent relapse

- first relapse for indolent lymphoma after first line therapy for relapse

- first relapse if immunosuppressive chemotherapy contraindicated

- with primary refractory disease or persistent disease after first line therapy of
relapse

- or lymphoma as a second malignancy e.g. a Richters transformation of CLL after
failing front line therapy

OR

GROUP D: Patients less than 18 yrs old

- with active disease in:

- second or subsequent relapse

- first relapse for indolent lymphoma after first line therapy for relapse

- first relapse if immunosuppressive chemotherapy contraindicated

- with primary refractory disease or persistent disease after first line therapy of
relapse

- with lymphoma as a second malignancy e.g. a Richters transformation of CLL after
failing front line therapy

2. Life expectancy of 6 weeks or greater.

3. Pulse oximetry of more than 95 percent on room air in patients who previously received
radiation therapy.

4. Karnofsky,Lansky score of 50 or greater.

5. Creatinine 2X or less of upper limit of normal for age.

6. Patients should have been off other investigational therapy for one month prior to
entry in this study.

7. Patients should have been off conventional therapy for at least 1 week prior to entry
in this study, including rituximab.

8. Patient and,or parent,guardian able to give informed consent.

9. Due to unknown effects of this therapy on a fetus, pregnant women are excluded from
this research. The male partner should use a condom. Females of child-bearing
potential should use of at least two forms of contraception unless female has had a
hysterectomy or tubal ligation.

10. Bilirubin 2X or less of upper limit of normal, AST 3X or less than the upper limit of
normal, and Hgb greater than or equal to 7.0

GROUP C (aza) Only:

11. Platelets greater than 25,000

Exclusion Criteria:

PROCUREMENT:

1. Patients with severe intercurrent infection.

2. Patients with active HIV infection at time of procurement (can be pending at the time
of blood draw).

3. Patients receiving systemic corticosteroids.

TREATMENT:

1. Patients with severe intercurrent infection.

2. Patients receiving systemic corticosteroids.

3. Pregnant breastfeeding.

4. Active viral infection with HIV or hepatitis type B or C. "Active" infection defined
as infectious disease testing indicating that patient blood is reactive for Hep B, C
and/or HIV and confirmed using PCR to measure viral load.

GROUP C (aza) Only:

5. Abnormal coagulation parameters (PT greater than 15 seconds, PTT greater than 40
seconds, and/or INR greater than 1.5)

6. Significant active cardiac disease within the previous 6 months including:

1. NYHA class 4 CHF

2. Unstable angina

3. Myocardial infarction

7. Known or suspected hypersensitivity to azacitidine or mannitol

8. Patients with advanced malignant hepatic tumors.