The goal of this clinical research study is to learn if CMC-544 given alone, and possibly given in combination with rituximab, can help to control the disease in patients with ALL. The safety of the study drug(s) will also be studied.

Study Drugs:

CMC-544 is a monoclonal antibody (a substance that can locate and bind to cancer cells). It is designed to attach to C22, a molecule that is found on most cancer cells with ALL. This may cause the cancer cells to die.

Rituximab is a monoclonal antibody that is designed to attach to leukemia cells and activate a series of events that may cause the cancer cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive CMC-544 by vein over about 60 minutes on Day 1 of each study "cycle" or over 60 minutes at a lowered dose on Days 1, 8 and 15 of each cycle, depending on when you joined the study. No matter what dosing schedule you are on, you will receive the same total dosage of CMC-544. Each study cycle is about 3-4 weeks.

If the disease is not responding to the CMC-544 after 2 cycles, you will begin receiving rituximab. On Day 1 of Cycle 3, you will receive rituximab by vein over about 8 hours. On Day 2 of Cycle 3, you will receive CMC-544 alone by vein over about 60 minutes. Then, starting on Day 1 of Cycle 4, you will begin receiving rituximab by vein over about 8 hours and CMC-544 by vein over about 60 minutes at least 2-4 hours after you receive the rituximab. You will receive this combination 1 time every week.

Your dose of the study drug(s) may change depending on any side effects you may have.

Study Visits:

You will have study visits within 1 week before Day 1 of each study cycle. At each study visit, the following tests and procedures will be performed:

• You will have a physical exam.
• Your performance status will be recorded.
• You will be asked how you are feeling and about any drugs you may be taking.
• You will have an ECG before you receive treatment with CMC-544 (+ 2 days).
• Blood (about 1 tablespoon) may be drawn to test how the study drug(s) may affect cancer cells before you receive the CMC-544 infusion.
• If you are receiving rituximab and if you have a history of irregular heartbeat or chest pain (due to heart trouble), you will have ECGs performed before the start of the rituximab, once during the infusion, and within 2 hours after the infusion. Rituximab infusion will be stopped if you experience any serious episodes of irregular heartbeat.
• If you are receiving rituximab, you may be examined for any signs or symptoms of bowel obstruction (blockage) and/or perforation (hole in the intestines, which may cause the contents to leak). Appropriate radiologic tests and surgical consults will be performed as needed.

Blood (about 1 tablespoon each time) will be drawn 1-3 times each week during Cycles 1 and 2, and at least 1 time every week during all other cycles for routine tests. Your doctor may decide to have more than 3 blood draws during Cycles 1 and 2.

You will have a bone marrow aspirate and/or biopsy between Days 14-21 (+/- 3 days) of Cycle 1 then every 1-2 cycles to check the status of the disease. You may have additional bone marrow aspirates and/or biopsies if your doctor feels it is necessary.

Length of Study:

You may receive CMC 544 with or without rituximab for up to 12 months. You will be taken off study if the disease gets worse or if you have intolerable side effects

Follow-up Visits:

You will have a follow-up visit 30 days after your last dose of the study drug(s). At this visit, you will be asked about any side effects you may be having. If you cannot make it to the clinic for this visit, it can be done over the phone with a member of the study staff. The phone call should last about 10 minutes.

This is an investigational study. Rituximab is FDA approved and commercially available for the treatment of lymphoid cancer. Neither CMC-544 nor the CMC-544/rituximab combination are FDA approved or commercially available. Their use in this study is investigational.

Up to 90 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Previously treated ALL (including Burkitt's lymphoma and lymphoblastic lymphoma) in relapse or primary refractory. Patients in first relapse will be eligible regardless of the first remission duration. At least 10 patients in Salvage 1-2 will be treated to assess anti-ALL response more precisely.
2. Age 16 years or older. Pediatric patients (<16 years old) will be allowed into the study after safety is established, that is at least 10 adult patients having received 1 or more cycles each.
3. Zubrod performance status 0-3.
4. Adequate liver function (bilirubin </= 1.5 mg/dL and Alanine transaminase (SGPT) or Aspartate transaminase (SGOT) </= 3 x upper limit of normal [ULN], unless considered due to tumor), and renal function (creatinine </= 2 mg/dL). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is </= 2.0 mg/dL and creatinine </= 3 mg/dL.
5. Male and female patients who are of childbearing potential agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 14 days of study start (applies only if patient is of childbearing potential. Non-childbearing is defined as >/= 1 year postmenopausal or surgically sterilized).

Exclusion Criteria:

1. Patient with active heart disease (NYHA class >/= 3 as assessed by history and physical examination).
2. Patients with a cardiac ejection fraction (as measured by either Radionuclide angiography (MUGA) or echocardiogram) < 45% are excluded.
3. Patients who receive other chemotherapy. Patients must have been off previous therapy for >/= 2 weeks and must have recovered from acute toxicity (to grade 1 or less) of all previous therapy prior to enrollment (consent signing). (Concurrent therapy for central nervous system [CNS] prophylaxis or treatment for CNS relapse is permitted). Treatment may start earlier if necessitated by the patient's medical condition (e.g. rapidly progressive disease) following discussion with the Principal Investigator.
4. Prior allogeneic stem cell transplant in previous 4 months.
5. Peripheral lymphoblasts > 50 x 10^9/L.
6. Pregnant and breast-feeding patients are excluded.
7. Patients with known hepatitis B are excluded.

Up to two years