Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00890656
• Collaborator: Enzon Pharmaceuticals, Inc. (Industry)
• Enrollment: 90
• Location: 1
• Arm: 1
• Duration (Months): 91
• Patients Per Site Per Month: 1

Study Details

Study Description

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

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 Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• 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: Jun 1, 2003
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

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 Names: Cytoxan ; Drug: Vincristine; 2 mg by vein (IV) weekly for 3: Days 1, 8, 15; Other Names: Oncovin® ; Drug: Doxorubicin; 50 mg/m^2 by vein (IV) over 24 hours; Other Names: Adriamycin® ; Drug: Decadron; 80 mg by vein (IV) or by mouth (P.O.) daily days 1-4 and 15-18; Other Names: Dexamethasone ; Drug: G-CSF; 10 mcg/kg/day (rounded) by vein (IV) or under the skin (subcutaneously) within 72 ± 48 hours; Other Names: 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 Names: 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 Names: 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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Remission [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• 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:

• Not Applicable

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson's website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00890656
• Other Study ID Numbers: ID03-0166
• First Posted: Apr 30, 2009
• Last Update Posted: Feb 20, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Acute Lymphoblastic Leukemia; ALL; Leukemia; Hyper-CVAD
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Dexamethasone; Cyclophosphamide; Doxorubicin; Methotrexate; Vincristine; Asparaginase; Pegaspargase

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 6/9/2003 to 10/12/2009. All patients registered at The University of Texas M.D. Anderson Cancer Center.

Arm/Group Title	Augmented Hyper-CVAD
Arm/Group Description	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.
Period Title: Overall Study
STARTED	90
COMPLETED	90
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Augmented Hyper-CVAD
Arm/Group Description	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.
Overall Participants	90
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	34
Sex: Female, Male (Count of Participants)
Female	40 44.4%
Male	50 55.6%
Region of Enrollment (participants) [Number]
United States	90 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Remission
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Augmented Hyper-CVAD
Arm/Group Description	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.
Measure Participants	90
Number [Participants]	41 45.6%

Adverse Events

Time Frame	7 years, 7 months
Arm/Group Title	Augmented Hyper-CVAD
Arm/Group Description	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.
All Cause Mortality
	Augmented Hyper-CVAD
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Augmented Hyper-CVAD
	Affected / at Risk (%)	# Events
Total	33/90 (36.7%)
Cardiac disorders
Cardiac other	1/90 (1.1%)	1
Hypotension	13/90 (14.4%)	13
Eye disorders
Visual loss	1/90 (1.1%)	1
Gastrointestinal disorders
GI hemmorrhage	2/90 (2.2%)	2
Dehydration	2/90 (2.2%)	2
Diarrhea	1/90 (1.1%)	1
General disorders
Death	9/90 (10%)	9
Pain	6/90 (6.7%)	6
Allergic reaction	2/90 (2.2%)	2
fever	4/90 (4.4%)	4
Infections and infestations
Neutropenic fever	8/90 (8.9%)	8
Infection	21/90 (23.3%)	21
Nervous system disorders
Syncope	1/90 (1.1%)	1
Renal and urinary disorders
Cystitis	1/90 (1.1%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/90 (1.1%)	1
Pulmonary embolism	1/90 (1.1%)	1
Other (Not Including Serious) Adverse Events
	Augmented Hyper-CVAD
	Affected / at Risk (%)	# Events
Total	57/90 (63.3%)
Endocrine disorders
hyperglycemia	17/90 (18.9%)	17
Gastrointestinal disorders
Nausea/Vomiting	32/90 (35.6%)	32
Diarrhea	23/90 (25.6%)	23
Mucositis	19/90 (21.1%)	19
General disorders
Pain	5/90 (5.6%)	5
Hepatobiliary disorders
Elevated liver function tests	29/90 (32.2%)	29
Nervous system disorders
Neuropathy	13/90 (14.4%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.