Study of Hyper-CVAD Plus Imatinib Mesylate for Philadelphia-Positive Acute Lymphocytic Leukemia
Phase II Study of Hyper-CVAD Plus Imatinib Mesylate (Gleevec, STI571) for Philadelphia-Positive Acute Lymphocytic Leukemia
2 other identifiers
interventional
54
1 country
1
Brief Summary
The goal of this clinical research study is to learn if intensive chemotherapy, combined with imatinib mesylate (Gleevec, STI571) given for 8 courses over 6 months, followed by maintenance imatinib mesylate plus chemotherapy for 2 years, followed by imatinib mesylate indefinitely can improve Philadelphia-positive acute lymphoblastic leukemia. The safety of this treatment will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 leukemia
Started Mar 2001
Longer than P75 for phase_2 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2001
CompletedFirst Submitted
Initial submission to the registry
June 3, 2002
CompletedFirst Posted
Study publicly available on registry
June 4, 2002
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2014
CompletedResults Posted
Study results publicly available
September 18, 2015
CompletedSeptember 18, 2015
August 1, 2015
13.3 years
June 3, 2002
August 19, 2015
August 19, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Response To Induction Therapy With Hyper-CVAD Plus Imatinib Mesylate
Complete Remission (CR): Defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count of 1.0 × 109/L or higher and a platelet count of 100 × 109/L and no extramedullary disease. Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts. Molecular CR: Same as for CR with RT-PCR negativity for bcr-abl. Induction Death: Defined as death occurring after start of therapy without meeting the definition of CR or resistant disease.
Baseline to 6 months
Disease-Free Survival Rate at 2-year and 5-year.
Disease-Free Survival (DFS) was calculated from the time of complete remission until relapse or death due to any cause.
Baseline to 2-year and 5-year
Secondary Outcomes (1)
Overall Survival Rate at 2-year and 5-year.
Baseline to 2-year and 5-year
Study Arms (1)
Hyper-CVAD + Imatinib
EXPERIMENTALImatinib 600 mg orally days 1-14, course 1, \& 600 mg daily days 1-14 (daily if tolerated course 1), even courses. Cyclophosphamide 300 mg/m\^2 intravenous (IV) for 6 doses days 1-3, odd courses. Doxorubicin 50 mg/m\^2 IV day 4; Vincristine 2 mg IV days 4 \& 11; \& Dexamethasone 40 mg IV or orally daily days 1-4 \& 11-14 odd courses 1, 3, 5, 7. Methotrexate 12 mg intrathecally (6 mg if via Ommaya reservoir) day 2, odd courses and 200 mg/m\^2 IV over 2 hours followed by 800 mg/m\^2 over 22 hours day 1 of even courses. Cytarabine 100 mg intrathecally day 7 for odd courses and 3 gm/m\^2 IV every 12 hours for 4 doses days 2-3 for even courses. Mesna 600 mg/m\^2 IV daily, odd courses. G-CSF 10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.
Interventions
600 mg by mouth on days 1 - 14 for course 1, and 600 mg by mouth daily days 1-14 (or daily if tolerated with course 1) for courses 2, 4, 6, 8.
300 mg/m\^2 by vein every 12 hours for 6 doses days 1, 2, 3 (total dose 1800 mg/m\^2) for courses 1, 3, 5, 7.
50 mg/m\^2 by vein on day 4 after last dose of CTX for courses 1, 3, 5, 7.
40 mg by vein or by mouth daily on days 1 - 4 and days 11 - 14 for courses 1, 3, 5, 7.
12 mg intrathecally (6 mg if via Ommaya reservoir) day 2 for courses 1, 3, 5, 7. 200 mg/m\^2 by vein over 2 hours followed by 800 mg/m\^2 over 22 hours on day 1 of courses 2, 4, 6, 8.
100 mg intrathecally day 7 for courses 1, 3, 5, 7. 3 gm/m2 by vein over 2 hrs every 12 hrs for 4 doses on days 2 and 3 for courses 2, 4, 6, 8.
600 mg/m\^2 by vein daily for 24 hours for courses 1, 3, 5, 7.
10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.
Eligibility Criteria
You may qualify if:
- Diagnosis of previously untreated Ph-positive ALL or previously treated in CR after 1-2 courses of therapy or failure after one course of induction chemotherapy without imatinib mesylate.
- Age \> or = 15 years. Those \< 15 years of age will be treated under compassionate IND.
- Zubrod performance status \< or = 2 (ECOG Scale, Appendix A).
- Adequate liver function (bilirubin \< or = to 3.0 mg/dl, unless considered due to tumor), and renal function (creatinine \< or = to 3.0 mg/dl, unless considered due to tumor).
- Adequate cardiac function as assessed clinically by physical examination.
- Signed informed consent.
You may not qualify if:
- Active serious infection not controlled by oral or intravenous antibiotics.
- Treatment with investigational antileukemic agent or chemotherapy agents in the last 7 days before study entry, unless full recovery from side-effects has occurred or patient has rapidly progressive disease judged life-threatening.
- Active secondary malignancy other than skin cancer (e.g. basal cell carcinoma or squamous cell carcinoma) than in investigator's opinion will shorten survival to less than 1 year.
- History of Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
- Prior history of treatment with imatinib mesylate.
- Pregnancy or lactating in women of childbearing potential.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Novartis Pharmaceuticalscollaborator
Study Sites (1)
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Ribera JM, Prawitz T, Freitag A, Sharma A, Dobi B, Rizzo F, Sabatelli L, Patos P. Ponatinib vs. Imatinib as Frontline Treatment for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Matching Adjusted Indirect Comparison. Adv Ther. 2023 Jul;40(7):3087-3103. doi: 10.1007/s12325-023-02497-y. Epub 2023 May 19.
PMID: 37208556DERIVEDDaver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, Garcia-Manero G, Borthakur G, Kadia T, Rytting M, Konopleva M, Kantarjian H, O'Brien S. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61. doi: 10.3324/haematol.2014.118588. Epub 2015 Feb 14.
PMID: 25682595DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Naval Daver, MD/Leukemia
- Organization
- The University of Texas (UT) MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Naval Daver, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 3, 2002
First Posted
June 4, 2002
Study Start
March 1, 2001
Primary Completion
July 1, 2014
Study Completion
July 1, 2014
Last Updated
September 18, 2015
Results First Posted
September 18, 2015
Record last verified: 2015-08