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Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)

This study is currently recruiting participants.
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Verified August 2017 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: June 9, 2011
Last updated: August 3, 2017
Last verified: August 2017

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.

Condition Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
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)

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.

Estimated Enrollment: 206
Actual Study Start Date: August 2011
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inotuzumab Ozogamycin + Low-Intensity Chemotherapy

Phase I:

Inotuzumab Ozogamycin on Day 3. 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 on Day 2 - cycles 1, 2, 3, and Intrathecal Ara-C on Day 8. Peg-filgrastim (neulasta) on Day 4.

Blinatumomab by vein on Days 1-29 of Cycles 5-6 and 11-12.

Phase II:

Inotuzumab Ozogamycin: 0.6mg/m2 per cycle given as divided doses 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 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: 0.6mg/m2 per cycle and given as divided doses in cycles 2 and 4 with 0.3mg/m2 given on days 2 and 8 as determined in Phase I.

Cycle is 28 days.

Other Name: CMC-544
Drug: 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: Rituxan
Drug: Cyclophosphamide
150 mg/m2 by vein over 3 hours twice a day Days 1 - 3 for Cycles 1, 3, 5, 7.
Other Names:
  • Cytoxan
  • Neosar
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: Mesnex
Drug: 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:
  • Oncovin
  • Vincristine Sulfate
  • Vincasar Pfs
Drug: Dexamethasone
20 mg by vein or by mouth on Days 1-4 and 11-14 of Cycles 1, 3, 5, 7.
Other Name: Decadron
Drug: Pegfilgrastim
6 mg subcutaneously on Day 4 of Cycles 1 - 8.
Other Names:
  • Neulasta
  • Peg-G-CSF
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:
  • Otrexup
  • Rasuvo
  • Rheumatrex
  • Trexall
  • Amethopterin
  • Methotrexate Sodium
  • MTX
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:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: 6-Mercaptopurine
6-Mercaptopurine 50 mg by mouth twice a day twice a day.
Other Names:
  • Mercaptopurine
  • Purinethol
  • 6-MP
Drug: Prednisone
Maintenance: Prednisone 50 mg by mouth daily for 5 days every month for 1 year.
Other Names:
  • Deltasone
  • Sterapred
  • Rayos
  • Meticorten
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.
Other Names:
  • Leucovorin
  • Wellcovorin
  • Calcium Leucovorin
  • Folinic Acid
  • Citrovorum Factor
Drug: Blinatumomab
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.

  Show Detailed Description


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients age 60 years or older with previously untreated ALL of pre-B, Philadelphia chromosome (Ph-) negative ALL. Minimal prior therapy (less than 1 week of steroids, vincristine, and/or 1 dose of anthracycline or alkylating agents) are allowed.
  2. Zubrod performance status 0-3.
  3. Adequate liver function (bilirubin </= 1.95 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 </= 2.6 mg/dL and creatinine </= 3 mg/dL.
  4. Provision of written informed consent.
  5. Patients in first remission are eligible.
  6. Patients with refractory-relapsed ALL of any age are eligible, provided they are not eligible for regimens of higher priority.

Exclusion Criteria:

  1. Ph-positive ALL, Burkitt's Leukemia or Lymphoma, T-cell ALL or lymphoblastic lymphoma.
  2. Patient with active heart disease (NYHA class >/= 3 as assessed by history and physical examination).
  3. Patients with a cardiac ejection fraction (as measured by either MUGA or echocardiogram) < 40% are excluded.
  4. Patients with active hepatitis are excluded.
  5. Pregnant or breast-feeding women are excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its 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
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Hagop Kantarjian, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01371630     History of Changes
Other Study ID Numbers: 2010-0991
NCI-2011-01123 ( Registry Identifier: NCI CTRP )
Study First Received: June 9, 2011
Last Updated: August 3, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Acute Lymphoblastic Leukemia
pre-B, Philadelphia chromosome (Ph-) negative
Maximum tolerated dose
Inotuzumab Ozogamycin
Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Antibodies, Bispecific
Folic Acid
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs processed this record on August 18, 2017