CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL)
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: CMC-544 (Inotuzumab Ozogamycin); Rituximab
Intervention description: First patients > 16 years and < 16 years receive CMC-544 at a dose of 1.3 mg/m^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m^2 IV over 1 hour every 4 week cycle.
Part 2 CMC-544 (Inotuzumab Ozogamycin) 0.8 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 1, 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 8, and 0.5 mg/m^2 IV over 1 hour (+ 15 minutes) on Day 15. Weekly doses can be given at + 1 day. Course may be repeated every 3 weeks. Rituximab will be given on Day 1 and CMC-544 on Day 2 of the first dose; with subsequent weekly doses, both will be given weekly, rituximab preceding CMC-544. The weekly dose of rituximab will be 375 mg/m2.; With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m^2 IV (by vein) over 2-6 hours every 3-4 weeks.
Intervention MeSH terms: Rituximab; Inotuzumab Ozogamicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: The study started as a single arm study of Inotuzumab Ozogamicin administered at two different dose levels. The protocol was later amended to modify to weekly Inotuxumab Ozogamicin administration.
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; Acute Lymphoblastic Leukemia; ALL; Burkitt's lymphoma; Lymphoblastic lymphoma; CMC-544; Inotuzumab Ozogamycin; Rituxan; Rituximab

Summary:

      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.
    

Eligibility criteria:

        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.