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A Phase II Study of Gleevec in Ph+ Chronic Phase Chronic Myelogenous Leukemia


Phase 2
N/A
21 Years
Not Enrolling
Both
Childhood Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia

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Trial Information

A Phase II Study of Gleevec in Ph+ Chronic Phase Chronic Myelogenous Leukemia


OBJECTIVES:

I. Determine the response rate in patients with Philadelphia chromosome positive chronic
phase chronic myelogenous leukemia treated with imatinib mesylate.

II. Determine the disease-free survival of patients treated with this drug. III. Determine
the pharmacokinetics of this drug in these patients. IV. Determine the toxic effects of this
drug in these patients. V. Determine the rates of hematological, cytogenetic, and molecular
response and time to response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (chronic
myelogenous leukemia [CML] in first chronic phase after failing interferon therapy or
demonstrating intolerance to interferon [closed to accrual as of 12/05/03] vs CML relapsing
after stem cell transplantation or in second or subsequent chronic phase [closed to accrual
as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior treatment [closed
to accrual as of 7/29/05] vs newly diagnosed CML in first chronic phase with no prior
treatment).

Patients receive oral imatinib mesylate once daily on days 1-28. Courses repeat every 28
days for 1 year in the absence of disease progression or unacceptable toxicity. Patients who
fail to achieve a complete hematologic response after 3 courses or a partial or complete
cytogenic response after 6 courses are removed from the study.

PROJECTED ACCRUAL: A total of 109 patients (30 for stratum I [closed to accrual as of
12/05/03] and stratum II [closed to accrual as of 7/29/05], 34 for stratum III [closed to
accrual as of 7/29/05], and 45 for stratum IV) will be accrued for this study within 2
years.


Inclusion Criteria:



- Diagnosis of Philadelphia chromosome positive (Ph+) chronic phase chronic myelogenous
leukemia (CML)

- Stratum I (closed to accrual as of 12/05/03):

- CML in first chronic phase with resistance to interferon alfa (IFN-A) therapy
defined as one of the following:

- WBC count at least 20,000/mm^3 after at least 3 months of treatment with an
IFN-A-containing regimen

- Rising WBC count (at least 100% increase to a level of at least
20,000/mm^3) by two samples at least two weeks apart while receiving
treatment with an IFN-A-containing regimen

- At least 66% Ph+ cells in bone marrow after 1 year of IFN-A therapy

- At least 30% increase in Ph+ cells in bone marrow after IFN-A-induced
cytogenetic response while continuing to receive IFN-A therapy

- Intolerance to interferon therapy defined as more than two grade 2 toxic effects
or any grade 3 toxic effect related to interferon therapy, except grade 3 fever,
that is persistent beyond the first 28-day course of therapy and unresponsive to
standard supportive care interventions

- Stratum II (closed to accrual as of 7/29/05): CML recurring after stem cell
transplantation or in second or subsequent chronic phase

- No molecular relapse (only evidence is detection of bcr-abl rearrangement with
normal bone marrow and blood morphology and normal standard cytogenetic
analysis)

- Stratum III (closed to accrual as of 7/29/05): Newly diagnosed CML in first chronic
phase with no prior treatment except hydroxyurea

- Stratum IV: Newly diagnosed CML in first chronic phase with no prior treatment except
hydroxyurea

- No accelerated or blast phase defined as one or more of the following:

- WBC doubling time less than 5 days

- Chloroma

- Medullary fibrosis

- More than 10% blasts in peripheral blood or bone marrow

- More than 20% promyelocytes in peripheral blood or bone marrow

- More than 20% basophils and eosinophils in peripheral blood

- Performance status - ECOG 0-2

- At least 8 weeks

- See Disease Characteristics

- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram

- Bilirubin no greater than 1.5 times normal

- ALT less than 3.0 times normal

- Albumin greater than 2 g/dL

- Creatinine no greater than 1.5 times normal

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No uncontrolled infection

- No CNS toxicity greater than grade 2

- See Disease Characteristics

- No prior immunotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
and stratum IV only)

- At least 3 months since prior stem cell transplantation (SCT) (patients with
allogeneic SCT must have no active graft-versus-host disease [GVHD] and have stable
use of steroids) (for patients in stratum II only )

- At least 1 week since prior growth factors

- At least 1 week since prior biologic therapy, including interferon alfa (for patients
in stratum I [closed to accrual as of 12/05/03] and stratum II only)

- Recovered from prior immunotherapy

- No concurrent immunomodulating agents

- See Disease Characteristics

- No prior chemotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
and stratum IV only)

- At least 6 weeks since prior busulfan or nitrosoureas

- At least 7 days since prior hydroxyurea

- At least 7 days since prior low-dose cytarabine (less than 30 mg/m^2 every 12 to 24
hours)

- At least 14 days since prior moderate-dose cytarabine (100-200 mg/m^2 for 5 to 7
days)

- At least 28 days since prior high-dose cytarabine (1-3 g/m^2 every 12 to 24 hours for
6 to 12 doses)

- At least 21 days since all other cytotoxic chemotherapy

- Recovered from prior chemotherapy

- No concurrent chemotherapy

- No concurrent steroids other than for controlled GVHD in patients with prior
allogeneic SCT

- No prior radiotherapy (for patients in stratum III [closed to accrual as of 7/29/05]
and stratum IV only)

- At least 2 weeks since prior local palliative (small port) radiotherapy*

- At least 3 months since prior craniospinal radiotherapy or radiotherapy to 50% or
more of pelvis*

- At least 6 weeks since prior substantial bone marrow radiotherapy*

- Recovered from prior radiotherapy

- No prior imatinib mesylate

- No concurrent enzyme-activating anticonvulsants

- No concurrent warfarin

- No concurrent naturopathic agents or herbal medicines

- No other concurrent investigational agents

- Concurrent low-molecular weight heparin allowed

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Martin Champagne

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01867

NCT ID:

NCT00030394

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Childhood Chronic Myelogenous Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Phase Chronic Myelogenous Leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase

Name

Location

Children's Oncology GroupArcadia, California  91006-3776