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A Phase I Study of CCI-779 in Combination With Imatinib Mesylate in Chronic Myelogenous Leukemia


Phase 1
18 Years
N/A
Not Enrolling
Both
Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia, Relapsing Chronic Myelogenous Leukemia

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Trial Information

A Phase I Study of CCI-779 in Combination With Imatinib Mesylate in Chronic Myelogenous Leukemia


OBJECTIVES:

I. Determine the safety and tolerability of temsirolimus when administered with imatinib
mesylate in patients with chronic myelogenous leukemia.

II. Determine potential dose-limiting toxic effects of this regimen in these patients.

III. Determine, preliminarily, hematologic and cytogenetic response rates in patients
treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of temsirolimus.

Patients receive temsirolimus intravenously (IV) over 30 minutes once on days 1, 8, 15, and
22 and oral imatinib mesylate once daily on days 1-28. Courses repeat every 28 days in the
absence of unacceptable toxicity or disease progression. Patients receive 2 additional
courses beyond maximal response. Cohorts of 3-6 patients receive escalating doses of
temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.


Inclusion Criteria:



- Histologically confirmed chronic myelogenous leukemia (CML)

- Philadelphia chromosome-positive OR Bcr-Abl-positive disease, meeting 1 of the
following criteria:

- Accelerated phase, defined by at least 1 of the following:

- 10-19% blasts in the peripheral blood or bone marrow

- At least 20% basophils in peripheral blood or bone marrow

- Platelet count < 100,000/mm^3 (unrelated to therapy)

- Platelet count > 1,000,000/mm^3 (unresponsive to therapy)

- Increasing splenomegaly AND increasing WBC count (unresponsive to
therapy)

- Clonal evolution

- Blast phase, defined by 1 of the following:

- At least 20% blasts in peripheral blood or bone marrow

- Extramedullary disease

- Chronic phase, defined by all of the following:

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

- Less than 20% basophils in peripheral blood or bone marrow

- Platelet count > 100,000/mm^3

- Absence of clonal evolution

- May have received and/or failed prior imatinib mesylate therapy

- Patients not previously treated with imatinib mesylate receive oral imatinib
mesylate once daily 14 days before beginning study drug

- Must be able to tolerate 600 mg per day of imatinib mesylate before
starting CCI-779

- Patients with chronic phase disease must have failed prior imatinib mesylate at
a dose ≥ 600 mg/day, as defined by 1 of the following:

- Must not have achieved or must have lost hematologic response within 3
months after the start of imatinib mesylate

- Must not have achieved or must have lost cytogenetic response after 6
months of treatment with imatinib mesylate

- Must not have achieved or must have lost major cytogenetic response after
12 months of treatment with imatinib mesylate

- Must have lost complete cytogenetic response

- Bone marrow aspirate and biopsy with cytogenetics and fluorescent in situ
hybridization confirming t(9;22) completed within the past 28 days

- Performance status - SWOG 0-2

- More than 3 months

- See Disease Characteristics

- Bilirubin normal

- AST and ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if suspected liver
involvement with leukemia)

- Creatinine normal

- Creatinine clearance > 60 mL/min

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Ejection fraction ≥ 50% by echocardiogram or MUGA scan for patients with known
positive cardiac history (e.g., heart failure, coronary artery disease, cardiomegaly
on prior chest x-ray, or valvular heart disease)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Fasting cholesterol ≤ 350 mg/dL

- Fasting triglycerides ≤ 400 mg/dL

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to temsirolimus or imatinib mesylate

- No active or ongoing infection

- No psychiatric illness or social situation that would preclude study compliance

- No other active malignancy except nonmelanoma skin cancer

- No other uncontrolled illness

- At least 48 hours since prior interferon alfa for CML

- At least 6 weeks since prior stem cell transplantation

- No concurrent biologic agents

- No concurrent prophylactic colony-stimulating factors

- At least 24 hours since prior hydroxyurea for CML

- At least 7 days since prior mercaptopurine or vinca alkaloids for CML

- At least 7 days since prior low-dose cytarabine (< 30 mg/m^2 every 12-24 hours) for
CML

- At least 14 days since prior homoharringtonine for CML

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

- At least 21 days since prior anthracyclines, mitoxantrone, cyclophosphamide,
etoposide, or methotrexate for CML

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

- At least 6 weeks since prior busulfan for CML

- No concurrent hydroxyurea

- No other concurrent chemotherapy

- At least 7 days since prior steroids for CML

- No prior organ transplantation

- More than 2 weeks since prior major surgery (e.g., thoracotomy or intra-abdominal
surgery)

- Recovered from all prior therapy

- Prior experimental therapy allowed provided completion of treatment corresponds to a
duration > 5 half-lives of the experimental drug or any known active metabolite
before study

- No concurrent cyclosporine

- No concurrent anagrelide

- No concurrent oral anticoagulants, including warfarin

- No concurrent CYP3A4 inducers or inhibitors

- No concurrent tacrolimus

- No concurrent plasmapheresis

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer therapies

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Unacceptable toxicity graded according to the NCI CTCAE version 3.0

Outcome Time Frame:

Up to 5 years

Safety Issue:

Yes

Principal Investigator

Tiong Ong

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California Medical Center At Irvine-Orange Campus

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00073

NCT ID:

NCT00101088

Start Date:

April 2005

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Blastic Phase Chronic Myelogenous Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Phase Chronic Myelogenous Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Blast Crisis
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase

Name

Location

University of California Medical Center At Irvine-Orange CampusOrange, California  92868