Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

This study has been completed.
Sponsor:
Collaborator:
Enzon Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00890656
First received: April 29, 2009
Last updated: February 17, 2012
Last verified: February 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 90
Study Start Date: June 2003
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Hide Detailed Description

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.

  Eligibility

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

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
  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: NCT00890656

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00890656     History of Changes
Other Study ID Numbers: ID03-0166
Study First Received: April 29, 2009
Results First Received: July 25, 2011
Last Updated: February 17, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Lymphoblastic Leukemia
ALL
Leukemia
Hyper-CVAD

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

ClinicalTrials.gov processed this record on July 29, 2014