CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL)
|Acute Lymphoblastic Leukemia||Drug: CMC-544 (Inotuzumab Ozogamycin) Drug: Rituximab||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) With CMC-544 (Inotuzumab Ozogamycin), With or Without Later Addition of Rituximab|
- Number of Patients with Response [ Time Frame: 4 week cycle ]Primary endpoint for efficacy is response which is defined as: Complete Remission (CR), Complete Remission without platelet recovery (CRp) or Partial Remission (PR).
|Actual Study Start Date:||June 2010|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: CMC-544 (Inotuzumab Ozogamycin)
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. 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.
Drug: CMC-544 (Inotuzumab Ozogamycin)
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.Drug: Rituximab
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.
Other Name: rituxan
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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.
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01134575
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||Hagop Kantarjian, MD||M.D. Anderson Cancer Center|