Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

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. Read our disclaimer for details. Identifier: NCT00890656
Recruitment Status : Completed
First Posted : April 30, 2009
Results First Posted : August 23, 2011
Last Update Posted : February 20, 2012
Enzon Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if a special combination of chemotherapy drugs called "augmented hyper-CVAD chemotherapy" given over 6 to 8 months followed by monthly maintenance chemotherapy for one year can help to control acute lymphoblastic leukemia or lymphoblastic lymphoma. The safety of this therapy will also be studied.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: Cyclophosphamide (CTX) Drug: Vincristine Drug: Doxorubicin Drug: Decadron Drug: G-CSF Drug: Methotrexate (MTX) Drug: Ara-C Drug: Pegaspargase Phase 2

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Detailed Description:

The augmented hyper-CVAD chemotherapy is a combination of chemotherapy drugs including cyclophosphamide, vincristine, adriamycin, dexamethasone, and pegaspargase given together for one "course" of treatment. It is called "augmented" because additional drugs are being added to the hyper-CVAD combination, which is the standard combination of chemotherapy drugs for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma. This switches back and forth with a course of the chemotherapy drugs methotrexate and ara-C (also with vincristine, dexamethasone, and pegaspargase).

Before treatment starts, you will have a physical exam, including blood (about 8 teaspoons) tests. You will also have a bone marrow sample taken; the sample will be taken through a large needle in the hipbone.

All participants will receive 2 kinds of chemotherapy courses for a total of 8 courses. Chemotherapy courses will be given through a large vein by a central venous catheter (a plastic tube usually placed under the collarbone).

During treatment, you will have a physical exam and give blood samples (about 1 tablespoon each) at least twice a week. A bone marrow sample will be repeated 2-3 weeks after the start of treatment to check the response, and later as needed.

Course 1 will include cyclophosphamide given by vein over 2-3 hours every 12 hours. This will be given for 6 doses over 3 days (Days 1, 2 and 3). Adriamycin will be given by vein over 24 hours on Day 4. Vincristine will be given by vein over 15 to 30 minutes on Days 1, 8, and 15. Dexamethasone (a steroid) will be given by mouth or by vein on Days 1 to 4 and 15-18. Pegaspargase will be given by vein over 1-2 hours on Day 1.

G-CSF (growth colony stimulating factor) will be given starting 24 hours after each course of chemotherapy is finished (Day 5 or 6). It is given to help with rapid recovery of the normal bone marrow. G-CSF will be injected by vein or under the skin until the blood counts recover.

Treatment to the brain will be given inside the spinal fluid (spinal tap) with ara-C and methotrexate on Days 2 and 7 of Courses 1 and 2 for a total of 4 treatments. This is done to decrease the risk that the leukemia will develop there.

During Course 2, you will receive methotrexate by infusion over 24 hours on the first day and ara-C by vein at a high dose over 2 hours every 12 hours for 4 doses (Days 2 and 3). You will also receive vincristine (Days 1, 8, and 15), dexamethasone (Days 1-4 and 15-18), and pegaspargase (Day 5).

Citrovorum factor (leucovorin), an antidote for side effects of methotrexate, will be given by vein or by mouth for 2-3 days (Day 2 and on). G-CSF will be given as in Course 1 (24 hours after the chemotherapy is finished). The treatment to the brain inside the spinal fluid will be given as in Course 1 on Days 2 and 7.

The schedule of chemotherapy will switch between hyper-CVAD (Courses 3, 5, and 7) and methotrexate/ara-C (Courses 4, 6 and 8) to complete a total of 8 courses. After the 8 courses, you will go on maintenance chemotherapy. This includes daily 6-mercaptopurine taken by mouth, weekly methotrexate by vein or mouth, monthly vincristine by vein, and prednisone by mouth for 5 days every month. Maintenance therapy will continue for one year.

Treatment will be given on an inpatient or outpatient basis for the 8 intensive courses of chemotherapy, as indicated by your condition. The maintenance treatments may be given as an outpatient. Patients will be taken off study if the disease gets worse or if intolerable side effects occur.

This is an investigational study. All of the drugs are commercially available. Their use together in this study is investigational. About 90 patients will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage
Study Start Date : June 2003
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Arm Intervention/treatment
Experimental: Augmented Hyper-CVAD
Hyper-CVAD (courses 1, 3, 5, and 7) alternated with high-dose methotrexate/ara-C (courses 2, 4, 6, and 8) administered on day 21; Hyper-CVAD = Cyclophosphamide, Vincristine, Doxorubicin, Decadron + Pegaspargase.
Drug: Cyclophosphamide (CTX)
300 mg/m^2 by vein (IV) over 3 hours every 12 hours for 6 doses days 1, 2, 3 of
Other Name: Cytoxan
Drug: Vincristine
2 mg by vein (IV) weekly for 3: Days 1, 8, 15
Other Name: Oncovin®
Drug: Doxorubicin
50 mg/m^2 by vein (IV) over 24 hours
Other Name: Adriamycin®
Drug: Decadron
80 mg by vein (IV) or by mouth (P.O.) daily days 1-4 and 15-18
Other Name: Dexamethasone
Drug: G-CSF
10 mcg/kg/day (rounded) by vein (IV) or under the skin (subcutaneously) within 72 ± 48 hours
Other Name: Neupogen®
Drug: Methotrexate (MTX)
200 mg/m2 by vein (IV) over 2 hours followed by 800 mg/m2 over 22 hours on day 1
Other Name: Rheumatrex®
Drug: Ara-C
3 gm/m^2 by vein (IV) over 2 hours every 12 hours for 4 doses on days 2 and 3.
Other Name: Cytosar-U®
Drug: Pegaspargase
2,500 units/m2 by vein (IV) on day 1 of odd courses and day 5 of even courses
Other Names:
  • PEG asparaginase
  • Oncaspar
  • Polyethylene Glycol Conjugated Lasparaginase-H

Primary Outcome Measures :
  1. Number of Participants With Complete Remission [ Time Frame: Response evaluated following first course at 14 -21 days and 1-2 weeks later to confirm response status (or at the time of hematologic recovery) and with visits every 2-3 courses. ]
    Complete remission (CR) required a marrow with ≤ 5% blasts in a normo- or hypercellular marrow with an absolute neutrophil count (ANC) of ≥ 1 * 10^9/L and a platelet count of ≥ 100 * 10^9/L with complete resolution of all sites of extramedullary disease required.

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

Inclusion Criteria:

  • Previously treated acute lymphoblastic leukemia (ALL) (including Burkitt's lymphoma) or lymphoblastic lymphoma in relapse or primary refractory;
  • No age restrictions;
  • Zubrod performance status </= 3;
  • Adequate liver (bilirubin </= 3mg/dl unless considered due to tumor) and renal function (creatinine </= 3mg/dl unless considered due to tumor);
  • Adequate cardiac function (New York Heart Association (NYHA) < III as assessed by history and physical examination)

Exclusion Criteria:

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): NCT00890656

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Enzon Pharmaceuticals, Inc.
Principal Investigator: Stefan F. Faderl, M.D. M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00890656     History of Changes
Other Study ID Numbers: ID03-0166
First Posted: April 30, 2009    Key Record Dates
Results First Posted: August 23, 2011
Last Update Posted: February 20, 2012
Last Verified: February 2012

Keywords provided by M.D. Anderson Cancer Center:
Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liposomal doxorubicin
BB 1101
Dexamethasone acetate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors