Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)
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.
|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||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|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)|
- 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.
|Actual Study Start Date:||August 2011|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: Inotuzumab Ozogamycin + Low-Intensity Chemotherapy
Starting dose of Inotuzumab Ozogamycin: 1.3 mg/m2 on Day 3; and 0.8 mg/m2 on Day 3 for subsequent cycles. Cyclophosphamide twice a day Days 1 - 3 for Cycles 1, 3, 5, 7. MESNA on Days 1-3 of Cycles 1, 3, 5, 7. Vincristine on Day 1 and 8. Dexamethasone on Days 1-4 and 11-14. Rituximab on Day 2 and 8 for cycles 1 and 3, as well as cycles 2 and 4. Intrathecal methotrexate 12 mg (6 mg via ommaya) on Day 2 - cycles 1, 2, 3, and Intrathecal Ara-C on Day 8. Peg-filgrastim (neulasta) on Day 4.
Dose level of Inotuzumab Ozogamycin: 1.0 mg/m2. Methotrexate on Day 1. Ara-C twice a day for 4 doses Days 2 and 3. Rituximab on Day 2 and 8 of cycles 2 and 4. Peg-filgrastim (neulasta) 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 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 (+/- 15 min) on Day 3 of the first cycle, then 0.8 mg/m2 by vein for Cycles 3, 5, 7 for a total of 4 doses.
Phase II: 1.3 mg/m2 by vein on Day 3 of Cycle 1 and 1.0 mg/m2 by vein on Day 2 or 3 for Cycles 2, 3, 4 as determined in Phase I.
Cycle is 28 days.
Other Name: CMC-544Drug: Rituximab
375 mg/m2 by vein on Day 2 and Day 8 of Cycles 1 - 4 per discretion of physician. The first dose of rituximab will be given as a slow infusion over 6-8 hours.
Other Name: RituxanDrug: Cyclophosphamide
150 mg/m2 by vein over 3 hours twice a day Days 1 - 3 for Cycles 1, 3, 5, 7.
Other Names:Drug: Mesna
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, 5, 7.
Other Name: MesnexDrug: Vincristine
2 mg by vein on Day 1 and Day 8 of Cycles 1, 3, 5, 7.
Maintenance: Vincristine 2 mg by vein monthly for 1 year
Other Names:Drug: Dexamethasone
20 mg by vein or by mouth on Days 1-4 and 11-14 of Cycles 1, 3, 5, 7.
Other Name: DecadronDrug: Pegfilgrastim
6 mg subcutaneously on Day 4 of Cycles 1 - 8.
Other Names:Drug: Methotrexate
Intrathecal methotrexate 12 mg (6 mg via ommaya) on Day 2 (+ 2 days) - cycles 1, 2, 3, and 4.
Methotrexate 50 mg/m2 by vein followed by 200 mg/m2 continuous infusion over approximately 22 hours on Day 1 for cycles 2, 4, 6, and 8.
Maintenance: Methotrexate 10 mg/m2 by mouth weekly for 3 years.
Other Names:Drug: Ara-C
Intrathecal ara-C 100 mg on Day 8 of cycles 1, 3, 5, 7.
Ara-C 0.5 g/m2 by vein twice a day for 4 doses - Days 2 and 3 of cycles 2, 4, 6, and 8.
Other Names:Drug: 6-Mercaptopurine
6-Mercaptopurine 50 mg by mouth twice a day twice a day.
Other Names:Drug: Prednisone
Maintenance: Prednisone 50 mg by mouth daily for 5 days every month for 1 year.
Other Names:Drug: Citrovorum
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, and 8.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01371630
|Contact: Hagop Kantarjian, MD||713-792-7026|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Hagop Kantarjian, MD||M.D. Anderson Cancer Center|