Inotuzumab Ozogamycin in Elderly Acute Lymphoblastic Leukemia (ALL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01371630
First received: June 9, 2011
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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 ALL. The safety of the study drugs will also be studied.

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-CVAD 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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-intensity Chemotherapy in Elderly 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 ] [ Designated as safety issue: Yes ]
    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.

  • Phase II: Progression-free survival (PFS) [ Time Frame: Baseline through 8 one-month treatments, up to 3 years or until disease progression ] [ Designated as safety issue: No ]

    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: 106
Study Start Date: August 2011
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: Inotuzumab Ozogamycin 1.3 mg/m2

Treatment of 8 induction - consolidation cycles low-intensity therapy with hyper-CVAD (Odd courses) alternating Methotrexate and Ara-C (even courses); and 8 Intrathecal prophylaxis doses twice per cycle in first 4 cycles. Rituximab 375 mg/m2 on Day 2 and Day 8 of first 4 cycles. Inotuzumab Ozogamycin dose level 1 of Cycle 1: 1.3 mg/m2 intravenous (IV) over 1 hour on Day 3; and 0.8 mg/m2 on Day 3 for subsequent cycles.

Hyper-CVAD includes a combination of cyclophosphamide, vincristine, dexamethasone, methotrexate, Ara-C (cytarabine), and Neulasta (pegfilgrastim).

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: 1.8 mg/m2 by vein on Day 3 of Cycle 1 and 1.3 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-544
Drug: Rituximab
375 mg/m2 by vein on Day 2 and Day 8 of Cycles 1 - 4. 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 24 hours, starting 1 hour prior to cyclophosphomide 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.
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 8 Cycles 1, 2, 3, and 4; and, 50 mg/m2 by vein over 2 hours, followed by 200 mg/m2 by continuous infusion over 22 hours on Day 1 of Cycles 2, 4, 6, 8.
Drug: Ara-C
Intrathecal Ara-C 100 mg on Day 2 of Cycles 1, 3, 5, 7; and, 0.5 g/m2 by vein over 3 hours twice a day on Days 2 and 3 for Cycles 2, 4, 6, 8.
Other Names:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Experimental: Phase II: Inotuzumab Ozogamycin 1.8 mg/m2
Low-intensity therapy with hyper-CVAD alternating Methotrexate and Ara-C in combination with second dose level Inotuzumab Ozogamycin 1.8 mg/m2 for Cycle 1, followed by 1.3 mg/m2 for subsequent cycles.
Drug: Rituximab
375 mg/m2 by vein on Day 2 and Day 8 of Cycles 1 - 4. 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 24 hours, starting 1 hour prior to cyclophosphomide 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.
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 8 Cycles 1, 2, 3, and 4; and, 50 mg/m2 by vein over 2 hours, followed by 200 mg/m2 by continuous infusion over 22 hours on Day 1 of Cycles 2, 4, 6, 8.
Drug: Ara-C
Intrathecal Ara-C 100 mg on Day 2 of Cycles 1, 3, 5, 7; and, 0.5 g/m2 by vein over 3 hours twice a day on Days 2 and 3 for Cycles 2, 4, 6, 8.
Other Names:
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </= 1.5 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.
  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. Currently study 2012-0151 (inotuzumab vs. intensive chemotherapy in ALL salvage 1 and 2) is an FDA pivotal trial and is a higher priority (September 10, 2012).

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 ClinicalTrials.gov identifier: NCT01371630

Contacts
Contact: Hagop Kantarjian, MD 713-792-7026

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Hagop Kantarjian, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01371630     History of Changes
Other Study ID Numbers: 2010-0991, NCI-2011-01123
Study First Received: June 9, 2011
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute Lymphoblastic Leukemia
ALL
Elderly
pre-B, Philadelphia chromosome (Ph-) negative
Maximum tolerated dose
Inotuzumab Ozogamycin
CMC-544
Vincristine
Rituximab
Rituxan
Cyclophosphamide
Cytoxan
Neosar
Dexamethasone
Decadron
Mesna
Mesnex
Pegfilgrastim
Neulasta
PEG-G-CSF
Methotrexate
Ara-C
Cytarabine
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Cytarabine
Rituximab
Dexamethasone
Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 18, 2014