Clinical trial NCT00250042: A Phase II Study of Gleevec and Arsenic Trioxide in Patients With CML Who Fail Gleevec
Official title: A Phase II Study of Gleevec and Arsenic Trioxide in Patients With CML Who Fail to Achieve a Complete Response to Initial Gleevec Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Other
Cancer
Lead sponsor: New Mexico Cancer Research Alliance
Sponsor class: OTHER
First posted: 2005-11-07
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 1.0 OBJECTIVES 1.1 To test the activity of arsenic trioxide in combination with imatinib in patients with CML with cytogenetic evidence of residual disease.

1.2 To determine the toxicity associated with this therapy.

Detailed description: * Chronic myelogenous leukemia (CML) results from the clonal expansion of immature myeloid cells with the t (9,22) (Ph) translocation, that encodes the constitutively active tyrosine kinase oncogene, bcr/abl. Patients with chronic phase CML are currently being treated with either hemopoetic stem cell transplantation (HSCT), or with the recently approved tyrosine kinase inhibitor, imatinib. Previous data, using interferon in patients with CML, has shown that patients who do not achieve a major cytogenetic response (defined as \>35% Ph+) have a shortened survival. These patients are often considered for HSCT. However, due to constraints of age, suitable donor, and patient choice, only a minority of patients will undergo this potentially curative procedure.
* The aim of this study is to create a uniform approach to the treatment of CML in New Mexico, with an aim of achieving complete cytogenetic response as the primary goal. A graded approach will be taken, starting out with the standard treatment (imatinib 400 mg per day), and then in patients identified as poor responders an imatinib, and arsenic combination will be offered to patients. It is hoped to find a complete cytogenetic response that exceeds the \~20% response with gleevec 800mg per day.

Eligibility criteria: Inclusion criteria:

* All patients, 18 years of age or older, with a diagnosis of CML.
* Patients must have a life expectancy of at least 12 weeks.
* Patients must have an ECOG performance status of 0-2.
* Patients must sign an informed consent.
* Patients should have adequate hepatic function with a total bilirubin \< 2 mg/dl and SGOT or SGPT \< two times the upper limit of normal, and adequate renal function as defined by a serum creatinine \< 1.5 x upper limit of normal.
* Patients with CML in chronic phase on gleevec as first line therapy who fulfill the following criteria:
* Failure to achieve a complete hematologic response (CHR) after 3 months of therapy (hematologic resistance)
* Failure to achieve a complete cytogenetic response (CGCR) after \> 9 months of therapy.
* Cytogenetic relapse, defined as an increase in the Ph+ cells by at least 30%.
* Hematologic relapse defined as the appearance of any of the following, confirmed by a second determination \> 1 month later:

  * WBC count \>20, 000,
  * Platelet count \>600,000,
  * Progressive splenomegaly \> 5 cm below the left intercostals margin,
  * \>5% myelocytes and/or metamyelocytes in the peripheral blood,
  * Blasts or promyelocytes in the peripheral blood

Exclusion Criteria:

* Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception.
* Patients may receive no other concurrent chemotherapy or radiation therapy during this trial.
* Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial.

Primary outcomes:
measure: To test the activity of arsenic trioxide in combination with imatinib in patients with CML with cytogenetic evidence of residual disease
timeFrame: 2 years
Secondary outcomes:
measure: To determine the toxicity associated with this therapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Santa Fe
country: United States
facility: New Mexico Cancer Care Associates
state: New Mexico
Study officials:
affiliation: University of New Mexico
name: Ian Rabinowitz, MD
role: PRINCIPAL_INVESTIGATOR
References: