CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL)

Tracking Information
First Submitted Date ICMJE	May 28, 2010
First Posted Date ICMJE	June 2, 2010
Last Update Posted Date	August 11, 2017
Actual Study Start Date ICMJE	June 2010
Estimated Primary Completion Date	June 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 28, 2010)	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).
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01134575 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL)
Official Title ICMJE	Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) With CMC-544 (Inotuzumab Ozogamycin), With or Without Later Addition of Rituximab
Brief 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.
Detailed Description	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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Acute Lymphoblastic Leukemia
Intervention ICMJE	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
Study Arms	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.; Interventions: Drug: CMC-544 (Inotuzumab Ozogamycin); Drug: Rituximab
Publications *	Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O'Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012 Apr;13(4):403-11. doi: 10.1016/S1470-2045(11)70386-2. Epub 2012 Feb 21.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: January 10, 2012)	90
Original Estimated Enrollment ICMJE; (submitted: May 28, 2010)	40
Estimated Study Completion Date	June 2019
Estimated Primary Completion Date	June 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 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.; 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.; Zubrod performance status 0-3.; Adequate liver function (bilirubin </= 1.5 mg/dL and SGPT or 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.; 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: Patient with active heart disease (NYHA class >/= 3 as assessed by history and physical examination).; Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) < 45% are excluded.; 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.; Prior allogeneic stem cell transplant in previous 4 months.; Peripheral lymphoblasts > 50 x 10^9/L.; Pregnant and breast-feeding patients are excluded.; Patients with known hepatitis B are excluded.
Sex/Gender	Sexes Eligible for Study: All
Ages	16 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01134575
Other Study ID Numbers ICMJE	2009-0872; NCI-2011-01699 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	M.D. Anderson Cancer Center
Study Sponsor ICMJE	M.D. Anderson Cancer Center
Collaborators ICMJE	Wyeth is now a wholly owned subsidiary of Pfizer
Investigators ICMJE	Study Chair: Hagop Kantarjian, MD M.D. Anderson Cancer Center
PRS Account	M.D. Anderson Cancer Center
Verification Date	August 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP