Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)
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|ClinicalTrials.gov Identifier: NCT01371630|
Recruitment Status : Recruiting
First Posted : June 13, 2011
Last Update Posted : April 27, 2018
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The goal of the Phase I part of this clinical research study is to test 2 dose levels of the drug inotuzumab ozogamycin to find the highest tolerable dose that can be given in combination with chemotherapy. The goal of Phase II is to learn if inotuzumab ozogamycin given in combination with chemotherapy can help to control acute lymphoblastic leukemia (ALL). The safety of the study drugs will also be studied.
Participants in this study are at least 60 years of age and have newly diagnosed ALL or have refractory-relapsed ALL regardless of age.
Inotuzumab ozogamycin is designed to attach to a protein that is often found in leukemia cells. This may cause the cancer cells to die.
Rituximab is designed to attach to cancer cells and damage them, which may cause the cells to die.
Hyper-CVD includes a combination of cyclophosphamide, vincristine, dexamethasone, methotrexate, Ara-C (cytarabine), and Neulasta (pegfilgrastim). The maintenance therapy used in this study is called POMP, which includes a combination of mercaptopurine, methotrexate, vincristine, and prednisone. These chemotherapy drugs are designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.
This is an investigational study. Inotuzumab ozogamycin, rituximab, Hyper-CVD, methotrexate, cytarabine, blinatumomab, and POMP maintenance drugs are FDA approved and commercially available for the treatment of leukemia. Combining inotuzumab ozogamycin with rituximab is investigational.
Up to 256 patients will take part in this study. All will be enrolled at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Acute Lymphoblastic Leukemia||Drug: Inotuzumab Ozogamycin Drug: Rituximab Drug: Cyclophosphamide Drug: Mesna Drug: Vincristine Drug: Dexamethasone Drug: Pegfilgrastim Drug: Methotrexate Drug: Ara-C Drug: 6-Mercaptopurine Drug: Prednisone Drug: Citrovorum Drug: Blinatumomab||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||256 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)|
|Actual Study Start Date :||August 2011|
|Estimated Primary Completion Date :||August 2019|
|Estimated Study Completion Date :||August 2019|
Experimental: Inotuzumab Ozogamycin + Low-Intensity Chemotherapy
Inotuzumab Ozogamycin on Day 2 and 8 of Cycles 1 and 3, and in Cycles 2 and 4. Cyclophosphamide twice a day Days 1 - 3 for Cycles 1, 3, 7, and 9. Vincristine on Day 1 and 8 of Cycles 1, 3, 7, and 9 . Rituximab on Day 1 and 8 for Cycles 1 and 3, and Cycles 2 and 4. Intrathecal methotrexate on Day 2 of Cycles 1 and 3 and on Day 8 of Cycles 2 and 4, and Intrathecal Ara-C on Day 8. Peg-filgrastim on Day 4.
Blinatumomab by vein on Days 1-29 of Cycles 5-6 and 11-12.
Inotuzumab Ozogamycin: 0.6mg/m2 per cycle in cycles 2 and 4 with 0.3mg/m2 given on days 2 and 8. Methotrexate on Day 1. Ara-C twice a day on Days 2 and 3. Rituximab on Day 2 and 8 of cycles 2 and 4. Peg-filgrastim on Day 4. Citrovorum rescue beginning 12 hrs post MTX completion.
Maintenance Therapy (3 years):
6-Mercaptopurine twice a day twice a day for three years. Methotrexate weekly for three years. Vincristine once a month for 1 year. Prednisone daily for 5 days every month for 1 year.
Drug: Inotuzumab Ozogamycin
Phase I: 1.3 mg/m2 by vein over 1 hour on Day 3 of the first cycle, then 0.8 mg/m2 by vein for for the following cycles for a total 4 inotuzumab ozogamycin doses.
Phase II: 1.3 mg/m2 om Day 3 of cycle 1, and 1.0 mg/mg2 on Day 2 or 3 of cycles 2, 3, and 4.
Dose Expansion: Inotuzumab ozogamycin during cycle 1 at a total dose of 0.9mg/m2 given as 0.6mg/m2 on Day 2 and 0.3 mg/m2 on Day 8. A total of 0.6 mg/m2 given during cycle 3 with 0.3 mg/m2 given on Days 2 and 8.
Cycle is 28 days.
Other Name: CMC-544
375 mg/m2 by vein on Day 1 and Day 8 of Cycles 1 and 3, and Cycles 2 and 4. per discretion of physician. The first dose of rituximab will be given as a slow infusion over 6-8 hours.
Other Name: Rituxan
150 mg/m2 by vein over 3 hours twice a day Days 1 - 3 for Cycles 1, 3, 7, and 9.
300 mg/m2 by vein continuous infusion daily for approximately 24 hrs, starting approximately 1 hour prior to cyclophosphamide and completing by approximately 12 hrs after the last dose of cyclophosphamide for Cycles 1, 3, 7, and 9.
Other Name: Mesnex
2 mg by vein on Day 1 and Day 8 of Cycles 1, 3, 7, and 9.
Maintenance: Vincristine 2 mg by vein monthly for 1 year
20 mg by vein or by mouth on Days 1-4 and 11-14 of Cycles 1, 3, 7, and 9.
Other Name: Decadron
6 mg subcutaneously on Day 4 of Cycles 1, 3, 7, and 9, and Cycles 2, 4, 8, and 10.
Intrathecal methotrexate 12 mg (6 mg via ommaya) on Day 2 (+ 2 days) Cycles 1 and 3.
Methotrexate 50 mg/m2 by vein followed by 200 mg/m2 continuous infusion over approximately 22 hours on Day 1 for cycles 2, 4, 8, and 10.
Maintenance: Methotrexate 10 mg/m2 by mouth weekly for 3 years.
Intrathecal ara-C 100 mg on Day 8 of cycles 1, and 3.
Ara-C 0.5 g/m2 by vein twice a day for 4 doses Days 2 and 3 of cycles 2, 4, 8, and 10.
Maintenance: 6-Mercaptopurine 50 mg by mouth twice a day twice a day.
Maintenance: Prednisone 50 mg by mouth daily for 5 days every month for 1 year.
Citrovorum rescue 50 mg by vein or mouth followed by 15 mg by vein or mouth every 6 hours for 8 doses beginning 12 hrs post MTX completion on Days 2-5 of Cycles 2, 4, 6, 8, and 10.
In the first induction cycle, initial dose of Blinatumomab is 9 μg/day for the first 4 days of treatment which then will be escalated (dose step) to 28 μg/day starting on day 5 through day 29 (week 4). For all subsequent cycles, 28 μg/day is the dose for all 4 weeks of continuous treatment.
- Phase I: Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamycin in Combination With Low-Intensity Chemotherapy [ Time Frame: With each 4 week study cycle ]
MTD defined by Dose Limiting Toxicities (DLTs) where DLTS observed in less than 2/6 participants treated at dose level 1 results in testing dose level 2 of inotuzumab ozogamycin. If DLTs are observed in < 2/6 patients treated, the second dose level is utilized for Phase II.
Dose limiting toxicities according to the NCI CTEP criteria
- Phase II: Progression-free survival (PFS) [ Time Frame: 2 years ]
Progression-free survival (PFS) was defined as the time between randomization and the date of first documented disease progression, relapse or death by any cause, whichever came first.
Bone marrow aspiration and/or biopsy (about 1 teaspoon) to check the status of the disease between Days 14-21 (+/- 3 days) of Cycle 1, and then every 2-4 cycles during consolidation.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01371630
|Contact: Elias Jabbour, MD||713-792-7026|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Elias Jabbour, MD||M.D. Anderson Cancer Center|