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LeukemiaPhase 2NCT00038610

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

A Phase 2 study testing Imatinib Mesylate, Cyclophosphamide and Doxorubicin in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Leukemia
What is being tested?
Imatinib Mesylate, Cyclophosphamide and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
Mar 2001to Jul 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase II Study of Hyper-CVAD Plus Imatinib Mesylate (Gleevec, STI571) for Philadelphia-Positive Acute Lymphocytic Leukemia

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.

Read the detailed description

Before treatment starts, patients will have a complete exam, including medical history and documentation of disease, blood, and marrow tests. A chest x-ray will be taken. CT scans may be taken if needed. A bone marrow sample will be taken through a large needle. An EKG and MUGA (heart function tests) will be performed.

During treatment, patients will give blood samples (about 1 tablespoon each) at least twice a week. A bone marrow sample will be repeated 2 and 3 weeks from the beginning of treatment to check on response. After two courses of chemotherapy, the tests done before treatment will be repeated to check for response.

All patients 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). Imatinib mesylate will be given as a pill with the chemotherapy.

Course 1 will start with cyclophosphamide given by vein over 2-3 hours every 12 hours for 6 doses over 3 days (Days 1,2,3). Mesna will be given by vein continuously for 4 days with the cyclophosphamide to protect the bladder. Doxorubicin will be given by vein over 24 hours on Day 4. Vincristine will be given by short infusion on Days 4 and 11. Dexamethasone (a steroid) will be given by mouth or by vein on Days 1-4 and 11-14. The imatinib mesylate will be given by mouth with breakfast and a large glass of water daily on Days 1-14. Medicines will be given to prevent nausea and to protect the kidneys from increased amounts of uric acid, which may be released when leukemia cells die.

G-CSF (growth stimulating colony factor) will be given after completion of the chemotherapy. It is given to allow for rapid recovery of the normal marrow. G-CSF will be injected under the skin until the counts recover. Treatment to the brain will be given inside the spinal fluid with methotrexate around Day 2 and cytarabine about day 7. This is done to prevent the leukemia from developing there.

For patients aged 60 years or older, this Course 1 will be given in a protective isolation room to decrease the risk of infection(s).

During Course 2, patients will be given methotrexate by infusion over 24 hours on the first day and cytarabine at a high dose over 2 hours every 12 hours for 4 doses (Days 2 and 3). 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). Solumedrol (a steroid) will be given by vein every 12 hours for 6 doses. Imatinib mesylate will be given by mouth with breakfast and a large glass of water on Days 1-14 or daily, depending on tolerance with Course 1. G-CSF will be given as in Course 1. The treatment to the brain inside the spinal fluid will be given as in Course 1 around Days 2 and 7.

The chemotherapy will alternate between hyper-CVAD plus imatinib mesylate (Courses 1, 3, 5, and 7) and methotrexate/cytarabine plus imatinib mesylate (Courses 2, 4, 6, and 8) to complete a total of 8 courses. G-CSF will be given as in Course 1. Anti-nausea medicine will be given with each course of chemotherapy. The urine will be alkalized to protect the kidneys. Antibiotics will be given by mouth to prevent infection.

After the 8 courses, monthly maintenance chemotherapy plus imatinib mesylate will be given. This includes daily imatinib mesylate, monthly vincristine by vein, and prednisone by mouth for 5 days every month. Maintenance chemotherapy will be given for a total of 24 months, and will be interrupted by 2 periods of intensive chemotherapy courses with hyper-CVAD and imatinib mesylate at 6 and 13 months from the start of maintenance. Imatinib mesylate will be continued daily as tolerated indefinitely.

After two courses of the intensive chemotherapy, the response to the treatment will be evaluated. If the leukemia is responding, the therapy will be continued. Patients will be taken off study if the leukemia starts to get worse.

During and after completion of treatment, patients will have a complete exam, including blood tests. If needed, a chest X-ray or CT scan will be done. A bone marrow sample will be taken through a large needle. Patients will then return every 2 to 3 months for a checkup, including blood and bone marrow. X-rays and heart studies (MUGA or ECG) may be repeated if needed.

An Ommaya reservoir may also be placed surgically as a route to treat leukemia in the brain or to prevent leukemia in patients who have difficulty with the spinal treatments. An Ommaya reservoir is an access port inserted under the skin of the scalp that enters into the spinal fluid cavity of the brain.

Treatment will be given on an inpatient basis (3 to 5 days) for the 8 intensive courses of chemotherapy, or as indicated by the clinical condition. The maintenance treatments will be given as an outpatient, except for the courses of hyper-CVAD and imatinib mesylate.

This is an investigational study. The FDA has approved imatinib mesylate for use in chronic myelogenous leukemia and other clinical research studies. About 55 patients will take part in this study. All will be from MD Anderson.

Conditions
Leukemia
Being tested
Imatinib Mesylate, Cyclophosphamide, Doxorubicin, Vincristine, Dexamethasone
Keywords
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
Medical subject headings
Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Imatinib MesylateDrug

    Also called Gleevec, Glivec, Imatinib, STI571

    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.

  • CyclophosphamideDrug

    Also called Cytoxan®,, Neosar®

    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.

  • DoxorubicinDrug

    Also called Adriamycin ®, Rubex ®, Adriamycin PFS, Adriamycin RDF

    50 mg/m^2 by vein on day 4 after last dose of CTX for courses 1, 3, 5, 7.

  • VincristineDrug

    2 mg by vein on day 4 and day 11 for courses 1, 3, 5, 7.

  • DexamethasoneDrug

    Also called Decadron

    40 mg by vein or by mouth daily on days 1 - 4 and days 11 - 14 for courses 1, 3, 5, 7.

  • MethotrexateDrug

    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.

  • CytarabineDrug

    Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

    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.

  • MesnaDrug

    Also called Mesnex

    600 mg/m^2 by vein daily for 24 hours for courses 1, 3, 5, 7.

  • G-CSFDrug

    Also called Filgrastim, Neupogen

    10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.

Study groups in NCT00038610
Study groupRoleWhat they receive
Hyper-CVAD + ImatinibExperimentalImatinib 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.
Receives: Drug: Imatinib Mesylate; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine; Drug: Mesna; Drug: G-CSF

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to 6 months

  2. 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.

    Measured: Baseline to 2-year and 5-year

Secondary outcomes (1)
  1. Overall Survival Rate at 2-year and 5-year.

    Overall survival (OS) was calculated from the date of initiation of therapy until death.

    Measured: Baseline to 2-year and 5-year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2002 (estimated)
  2. Study startMar 2001
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00038610
Sponsor's protocol ID
ID01-006
Other IDs
NCI-2012-01487
Status last verified
Aug 2015
First submitted
3 Jun 2002
Last updated
18 Sep 2015
Data monitoring committee
No

Publications

  • 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.

    PubMed 37208556
  • Daver 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.

    PubMed 25682595

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Imatinib Mesylate, Cyclophosphamide and Doxorubicin in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response To Induction Therapy With Hyper-CVAD Plus Imatinib Mesylate (time frame: Baseline to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00038610, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2015.

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