Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) With CMC-544 (Inotuzumab Ozogamycin), With or Without Later Addition of Rituximab


Phase 1
16 Years
N/A
Open (Enrolling)
Both
Acute Lymphoblastic Leukemia

Thank you

Trial Information

Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) With CMC-544 (Inotuzumab Ozogamycin), With or Without Later Addition of Rituximab


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 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
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 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients with Response

Outcome Description:

Primary endpoint for efficacy is response which is defined as: Complete Remission (CR), Complete Remission without platelet recovery (CRp) or Partial Remission (PR).

Outcome Time Frame:

4 week cycle

Safety Issue:

No

Principal Investigator

Hagop Kantarjian, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2009-0872

NCT ID:

NCT01134575

Start Date:

June 2010

Completion Date:

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Relapsed
  • Refractory
  • Acute Lymphoblastic Leukemia
  • ALL
  • Burkitt's lymphoma
  • Lymphoblastic lymphoma
  • CMC-544
  • Inotuzumab Ozogamycin
  • Rituxan
  • Rituximab
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location
UT MD Anderson Cancer Center Houston, Texas  77030