Study of Hyper-CVAD Plus Imatinib Mesylate for Philadelphia-Positive Acute Lymphocytic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00038610
First received: June 3, 2002
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Imatinib Mesylate
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Dexamethasone
Drug: Methotrexate
Drug: Cytarabine
Drug: Mesna
Drug: G-CSF
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 Hyper-CVAD Plus Imatinib Mesylate (Gleevec, STI571) for Philadelphia-Positive Acute Lymphocytic Leukemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Patients with Event-Free Survival After Hyper-CVAD Plus Imatinib Mesylate [ Time Frame: Baseline to 2 Years ] [ Designated as safety issue: Yes ]

    Disease-free survival is the time from documented complete remission (CR) until relapse or death. Event-free survival is the time from treatment until any failure (resistant disease, relapse, or death). Results compared descriptively to historical controls in terms of response, survival, toxicity, etc. Confidence intervals will be broad, ie., 95% confidence interval width of approximately 20% for CR rate estimate.

    Complete Remission (CR): Normalization of peripheral blood and bone marrow with 5% or less blasts in normocellular or hypercellular marrow with a granulocyte count of 1 x 109/L or above, and platelet count of 100 x 109/L. Complete resolution of all sites of extramedullary disease is required for CR.

    Molecular CR: Same as for CR with RT-PCR negativity for bcr-abl.

    Partial Response (PR): As above for CR except for the presence of 6-25% marrow blasts.



Enrollment: 54
Study Start Date: March 2001
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hyper-CVAD + Imatinib
Imatinib 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. Cyclophosphamide 300 mg/m2 by vein for 6 doses days 1, 2, 3 for courses 1, 3, 5, 7. Doxorubicin 50 mg/m2 by vein on day 4 for courses 1, 3, 5, 7. Vincristine 2 mg by vein on day 4 and day 11 for courses 1, 3, 5, 7. Dexamethasone 40 mg by vein or by mouth daily on days 1 - 4 and days 11 - 14 for courses 1, 3, 5, 7. Methotrexate 12 mg intrathecally (6 mg if via Ommaya reservoir) day 2 for courses 1, 3, 5, 7. and 200 mg/m2 by vein over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 of courses 2, 4, 6, 8. Cytarabine 100 mg intrathecally day 7 for courses 1, 3, 5, 7, and 3 gm/m2 by vein every 12 hrs for 4 doses on days 2 and 3 for courses 2, 4, 6, 8. Mesna 600 mg/m2 by vein daily for courses 1, 3, 5, 7. G-CSF 10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.
Drug: Imatinib Mesylate
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.
Other Names:
  • Gleevec
  • Glivec
  • Imatinib
  • STI571
  • STI-571
  • CGP-57148B
  • NSC-716051
Drug: Cyclophosphamide
300 mg/m2 by vein every 12 hours for 6 doses days 1, 2, 3 (total dose 1800 mg/m2) for courses 1, 3, 5, 7.
Other Names:
  • Cytoxan®,
  • Neosar®
Drug: Doxorubicin
50 mg/m2 by vein on day 4 after last dose of CTX for courses 1, 3, 5, 7.
Other Names:
  • Adriamycin ®
  • Rubex ®
  • Adriamycin PFS
  • Adriamycin RDF
Drug: Vincristine
2 mg by vein on day 4 and day 11 for courses 1, 3, 5, 7.
Drug: Dexamethasone
40 mg by vein or by mouth daily on days 1 - 4 and days 11 - 14 for courses 1, 3, 5, 7.
Other Name: Decadron
Drug: Methotrexate

12 mg intrathecally (6 mg if via Ommaya reservoir) day 2 for courses 1, 3, 5, 7.

200 mg/m2 by vein over 2 hrs followed by 800 mg/m2 over 22 hrs on day 1 of courses 2, 4, 6, 8.

Drug: Cytarabine

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.

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
Drug: Mesna
600 mg/m2 by vein daily for 24 hours for courses 1, 3, 5, 7.
Other Name: Mesnex
Drug: G-CSF
10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.
Other Names:
  • Filgrastim
  • Neupogen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age > or = 15 years. Those < 15 years of age will be treated under compassionate IND.
  3. Zubrod performance status < or = 2 (ECOG Scale, Appendix A).
  4. 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).
  5. Adequate cardiac function as assessed clinically by physical examination.
  6. Signed informed consent.

Exclusion Criteria:

  1. Active serious infection not controlled by oral or intravenous antibiotics.
  2. 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.
  3. 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.
  4. History of Grade III/IV cardiac problems as defined by the New York Heart Association Criteria.
  5. Prior history of treatment with imatinib mesylate.
  6. Pregnancy or lactating in women of childbearing potential.
  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: NCT00038610

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis Pharmaceuticals
Investigators
Principal Investigator: Naval Daver, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00038610     History of Changes
Other Study ID Numbers: ID01-006, NCI-2012-01487
Study First Received: June 3, 2002
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Lymphoblastic
Acute
Philadelphia-Positive
Imatinib Mesylate
Gleevec
Glivec
Imatinib
STI571
STI-571
CGP-57148B
NSC-716051
Cyclophosphamide
Cytoxan®,
Neosar®
Doxorubicin
Adriamycin ®
Rubex ®
Adriamycin PFS
Adriamycin RDF
Vincristine
Dexamethasone
Decadron
Methotrexate
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride
Mesna

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
Mesna
Cyclophosphamide
Cytarabine
Methotrexate
Liposomal doxorubicin
Imatinib
Dexamethasone
Doxorubicin
Vincristine
Lenograstim
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on August 19, 2014