CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

Study Drug Administration:

The dose of inotuzumab ozogamicin you receive will depend on when you joined this study. The
first group of 2 participants will receive the lowest dose level of inotuzumab ozogamicin.
Each new group will receive a higher dose of inotuzumab ozogamicin than the group before it,
if no intolerable side effects were seen. Three (3) dose levels will be tested.

For a stem cell transplant, the days before you receive your stem cells are called minus
days. The day you receive the stem cells is called Day 0. The days after you receive the stem
cells are called plus days.

On Day -13, you will receive inotuzumab ozogamicin by vein over 1 hour.

On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you. If
you have a CD20-positive cancer, you will receive rituximab by vein over 4-6 hours.

On Days -5, -4- and -3, you will receive fludarabine by vein over about 1 hour and
bendamustine by vein over about 30 minutes to 1 hour.

On Days -2 and -1, if you will be receiving a matched unrelated donor's (MUD) stem cells, you
will receive ATG by vein over 3-4 hours. If you will be receiving a related donor's stem
cells, you will "rest" (you will not receive chemotherapy drugs). ATG is given to suppress
the immune system.

Beginning on Day -2, you will receive tacrolimus as a continuous (nonstop) infusion until you
are able to take it by mouth. Tacrolimus is given to help prevent transplant rejection.

On Day 0, you will receive the stem cell transplant by vein.

On Days +1 and +8, if you have a CD20 positive cancer, you will receive rituximab by vein
over 4-6 hours.

On Days +1, +3, and +6, you will receive methotrexate by vein over 30 minutes. Methotrexate
is given to help prevent graft versus host disease (GVHD).

On Day +11, if you received a transplant from a MUD, you will receive methotrexate by vein
over about 30 minutes.

When you are able to take tacrolimus by mouth, you will take it once or twice a day for about
6 months and then your doctor will tell you how to taper it off (gradually stop taking it).

You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week
after the transplant, until your blood cell levels return to normal. Filgrastim is designed
to help with the growth of white blood cells.

If the disease does not respond to treatment or gets worse, you will receive rituximab and a
donor lymphocyte infusion containing T-cells by vein over 10-30 minutes.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Study Visits:

Before Day -13:

- Blood (about 4 tablespoons) will be drawn for routine tests, to test for infectious
diseases, such as HIV and hepatitis, and to check the status of the disease.

- You will have a bone marrow aspiration and biopsy to check the status of the disease. To
collect a bone marrow aspiration/biopsy, an area of the hip or other site is numbed with
anesthetic, and a small amount of bone marrow and bone is withdrawn through a large
needle.

- You will have a chest x-ray.

- You will have a computed tomography (CT) scan of your neck, chest, abdomen, and pelvis.

- If your doctor thinks it is needed, you will have positron emission tomography (PET)
scan.

- If you have had Gilbert's Disease, you will have an abdominal ultrasound.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. After you are sent home from the hospital, you must remain in the Houston area to
be checked for infections and other transplant side effects until about 3 months after
transplant. During this time, you will return to the clinic at least 1 time each week. The
following tests and procedures will be performed:

- You will be asked about how you are feeling and about any side effects you may be
having.

- Blood (about 2 teaspoons) will be drawn for routine tests.

About 1, 3, 6, and 12 months after transplant and, if your doctor thinks it is needed, at
Years 2 and 3:

- You will have a physical exam, including measurement of your weight.

- You will be asked about how you are feeling and about any side effects you may be having
and drugs you may be taking.

- Blood (about 2 teaspoons) will be drawn for routine tests, to check the status of the
disease, and to learn how the transplant has taken.

- If your doctor thinks it is needed, you will have a bone marrow aspiration and biopsy to
check the status of the disease,

- You will have a CT scan of your neck, chest, abdomen, and pelvis.

- If your doctor thinks it is needed, you will have a PET scan.

Length of Study:

You will be on study for up to about 3 years. You may be taken off study early if the disease
gets worse, if you have any intolerable side effects, if you are unable to follow study
directions, if your doctor thinks it is in your best interest, if the study is stopped, or if
you choose to leave the study early.

You should talk to the study doctor if you want to leave the study early. If you are taken
off study early, you still may need to return for routine post-transplant follow-up visits,
if your transplant doctor decides it is needed.

If you are thinking about dropping out of this study, please tell the study doctor. The
doctor can tell you about the effects of stopping treatment. You and the doctor can talk
about what follow-up care and testing would help you the most.

If you leave the study, your test results and information cannot be removed from the study
records.

Inclusion Criteria:

1. Age 18 to 70 years of age.

2. Patients with B-cell hematological malignancies who are eligible for allogeneic
transplantation.

3. Patients must have a fully-matched sibling donor or a matched unrelated donor
identified.

4. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.

5. Left ventricular EF >/= 45% with no uncontrolled arrhythmias or symptomatic heart
disease.

6. FEV1, FVC >/= 50% and corrected DLCO >/= 50%.

7. Serum creatinine <1.6 mg/dL. Serum bilirubin < 2 mg/dL upper limit of normal (unless
due to Gilbert's Disease; patient with this disease should have a right upper quadrant
ultrasound evaluation before treatment).

8. SGPT < 2 X upper limit of normal.

9. Men and women of reproductive potential must agree to follow accepted birth control
methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
spermicide, condom with spermicide, or abstinence) for the duration of the study.

10. Negative Beta HCG test in a woman with child bearing potential defined as not
post-menopausal for 12 months or no previous surgical sterilization) or currently
breast-feeding. Pregnancy testing is not required for post-menopausal or surgically
sterilized women.

Exclusion Criteria:

1. Patient with active CNS involvement.

2. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.

3. Patients with other malignancies diagnosed within 2 years prior to study registration.
Skin squamous or basal cell carcinoma are exceptions.

4. Active bacterial, viral or fungal infections.

5. History of stroke within 6 months.

6. History of biliary colic attack.

7. A prior autologous transplant within 3 months of study entry or allogeneic stem cell
transplant.

8. Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

9. Patient has received other investigational drugs within 3 weeks before study
registration.

10. Serious nonmalignant disease which, in the opinion of the investigator would
compromise protocol objectives.

11. Prior exposure to CMC-544 within past 6 months.

12. Established refractoriness to CMC-544.