Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

NCT ID: NCT00890656

Last Updated: 2012-02-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-06-30

Study Completion Date

2011-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cyclophosphamide (CTX)

Intervention Type DRUG

300 mg/m\^2 by vein (IV) over 3 hours every 12 hours for 6 doses days 1, 2, 3 of

Vincristine

Intervention Type DRUG

2 mg by vein (IV) weekly for 3: Days 1, 8, 15

Doxorubicin

Intervention Type DRUG

50 mg/m\^2 by vein (IV) over 24 hours

Decadron

Intervention Type DRUG

80 mg by vein (IV) or by mouth (P.O.) daily days 1-4 and 15-18

G-CSF

Intervention Type DRUG

10 mcg/kg/day (rounded) by vein (IV) or under the skin (subcutaneously) within 72 ± 48 hours

Methotrexate (MTX)

Intervention Type DRUG

200 mg/m2 by vein (IV) over 2 hours followed by 800 mg/m2 over 22 hours on day 1

Ara-C

Intervention Type DRUG

3 gm/m\^2 by vein (IV) over 2 hours every 12 hours for 4 doses on days 2 and 3.

Pegaspargase

Intervention Type DRUG

2,500 units/m2 by vein (IV) on day 1 of odd courses and day 5 of even courses

Interventions

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Cyclophosphamide (CTX)

300 mg/m\^2 by vein (IV) over 3 hours every 12 hours for 6 doses days 1, 2, 3 of

Intervention Type DRUG

Vincristine

2 mg by vein (IV) weekly for 3: Days 1, 8, 15

Intervention Type DRUG

Doxorubicin

50 mg/m\^2 by vein (IV) over 24 hours

Intervention Type DRUG

Decadron

80 mg by vein (IV) or by mouth (P.O.) daily days 1-4 and 15-18

Intervention Type DRUG

G-CSF

10 mcg/kg/day (rounded) by vein (IV) or under the skin (subcutaneously) within 72 ± 48 hours

Intervention Type DRUG

Methotrexate (MTX)

200 mg/m2 by vein (IV) over 2 hours followed by 800 mg/m2 over 22 hours on day 1

Intervention Type DRUG

Ara-C

3 gm/m\^2 by vein (IV) over 2 hours every 12 hours for 4 doses on days 2 and 3.

Intervention Type DRUG

Pegaspargase

2,500 units/m2 by vein (IV) on day 1 of odd courses and day 5 of even courses

Intervention Type DRUG

Other Intervention Names

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Cytoxan Oncovin® Adriamycin® Dexamethasone Neupogen® Rheumatrex® Cytosar-U® PEG asparaginase Oncaspar Polyethylene Glycol Conjugated Lasparaginase-H

Eligibility Criteria

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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

* Not Applicable
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Enzon Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stefan F. Faderl, M.D.

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://mdanderson.org

M.D. Anderson's website

Other Identifiers

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ID03-0166

Identifier Type: -

Identifier Source: org_study_id

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