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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01371630
Recruitment Status : Recruiting
First Posted : June 13, 2011
Last Update Posted : April 27, 2018
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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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)
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)
Actual Study Start Date : August 2011
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Arm Intervention/treatment
Experimental: Inotuzumab Ozogamycin + Low-Intensity Chemotherapy

Phase I:

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.

Phase II:

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

Drug: Rituximab
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

Drug: Cyclophosphamide
150 mg/m2 by vein over 3 hours twice a day Days 1 - 3 for Cycles 1, 3, 7, and 9.
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, 7, and 9.
Other Name: Mesnex

Drug: Vincristine

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

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, 7, and 9.
Other Name: Decadron

Drug: Pegfilgrastim
6 mg subcutaneously on Day 4 of Cycles 1, 3, 7, and 9, and Cycles 2, 4, 8, and 10.
Other Names:
  • Neulasta
  • Peg-G-CSF

Drug: Methotrexate

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.

Other Names:
  • Otrexup
  • Rasuvo
  • Rheumatrex
  • Trexall
  • Amethopterin
  • Methotrexate Sodium
  • MTX

Drug: Ara-C

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.

Other Names:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Drug: 6-Mercaptopurine
Maintenance: 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, 8, and 10.
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.

Primary Outcome Measures :
  1. 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

  2. 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.

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Ages Eligible for Study:   Child, Adult, Older Adult
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its 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
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Elias Jabbour, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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 )
First Posted: June 13, 2011    Key Record Dates
Last Update Posted: April 27, 2018
Last Verified: April 2018

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