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Clinical Trials (PDQ®)

Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IBiomarker/Laboratory analysis, TreatmentCompleted18 and overNCINCI-2009-00056
NCI-6383, CDR0000401509, MC0313, 6383, U01CA070095, U01CA069912, MAYO-MC0313, NCT00098423

Trial Description

Summary

This phase I trial is studying the side effects and best dose of tanespimycin when given with cytarabine in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia, or myelodysplastic syndromes. Drugs used in chemotherapy, such as tanespimycin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tanespimycin may also help cytarabine kill more cancer cells by making cancer cells more sensitive to the drug. Giving tanespimycin together with cytarabine may kill more cancer cells.

Further Study Information

OBJECTIVES:

I. Determine the maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin) when administered with cytarabine in patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic myelomonocytic leukemia, or high-grade myelodysplastic syndromes.

II. Determine the toxic effects of this regimen in these patients. III. Determine, preliminarily, the activity of this regimen in these patients. IV. Correlate the pharmacokinetics of this regimen with cytochrome p450 3A5 genotype in these patients.

V. Determine the effect of this regimen on client proteins in vivo and ex vivo using leukemic blasts from patients treated with this regimen.

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

Patients receive induction therapy comprising cytarabine intravenously (IV) continuously on days 1-5 and tanespimycin IV over 1 hour on days 3 and 6.

Patients achieving a morphologic complete response with incomplete blood count recovery (CRi) or partial response may be eligible to receive a second induction course of therapy after day 21 at the discretion of the principal investigator. Patients achieving a complete response (CR) receive up to 4 courses of consolidation therapy with cytarabine and tanespimycin. Consolidation therapy repeats approximately every 60 days in the absence of disease progression or unacceptable toxicity. Patients who achieve CR and remain in remission for ≥ 6 months may be retreated with cytarabine and tanespimycin (at the current dose level or the maximum tolerated dose [MTD]) at the time of relapse. Cohorts of 3-6 patients receive escalating doses of tanespimycin until the 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 at 3 months.

Eligibility Criteria

Inclusion Criteria:

  • Diagnosis of 1 of the following:
  • Acute myeloid leukemia, except acute promyelocytic leukemia (M3 disease), meeting 1 of the following criteria:
  • Failed to achieve complete remission (CR) after initial induction therapy regimen*
  • First relapse within 1 year of initial CR
  • Failed re-induction therapy at first or second relapse
  • Second or third relapse after completing ≤ 3 different induction therapy regimens
  • Antecedent hematologic disorder (myelodysplastic syndromes [MDS], chronic myeloproliferative disease, or chronic myelomonocytic leukemia [CMML])
  • Received prior chemotherapy for a non-hematologic malignancy
  • High-risk cytogenetic abnormalities (abnormalities of chromosome 5, 7, 8, or 11 OR ≥ 3 karyotypic abnormalities)
  • Acute lymphoblastic leukemia, meeting 1 of the following criteria:
  • Failed to achieve CR after initial induction therapy regimen
  • First relapse within 1 year of initial CR
  • Failed re-induction therapy at first or second relapse
  • Second or third relapse after completing ≤ 3 different induction therapy regimens
  • Chronic myelogenous leukemia, meeting the following criteria:
  • Accelerated OR blast phase (> 10% increase in the blast percentage in bone marrow)
  • Failed prior imatinib mesylate
  • No more than 1 prior chemotherapy regimen in addition to imatinib mesylate
  • CMML, meeting the following criteria:
  • More than 10% increase in blast percentage AND organ infiltration OR impending marrow failure as evidenced by cytopenia
  • No t(5;12) by cytogenetics (unless failed prior trial of imatinib mesylate)
  • High-grade MDS, defined as > 10% blasts on marrow cellularity (refractory anemia with excess blasts in transformation) OR International Prognostic Scoring System MDS prognostic score > 1.5
  • Not a candidate for allogenic bone marrow transplantation* from a related sibling donor (i.e., HLA-identical sibling)
  • No known standard or potentially curative therapy exists or is capable of extending life expectancy
  • No clinical symptoms suggesting CNS leukemia
  • Performance status - ECOG 0-2
  • At least 60 days
  • See Disease Characteristics
  • Bilirubin ≤ 1.5 times upper limit of normal (unless attributed to underlying disease)
  • Creatinine clearance ≥ 60 mL/min
  • No New York Heart Association class III-IV heart failure
  • No myocardial infarction within the past year
  • LVEF ≥ 40% by MUGA
  • No cardiac symptoms ≥ grade 2
  • No uncontrolled dysrhythmia requiring medication
  • No poorly controlled angina
  • QTc ≤ 450 msec for men and ≤ 470 msec for women
  • No congenital long QT syndrome
  • No left bundle branch block
  • No ischemic heart disease within the past 6 months
  • No history of cardiac toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine
  • No other significant cardiac disease
  • No active uncontrolled infection
  • No history of serious allergic reaction to eggs
  • No known HIV infection or AIDS (with or without highly active antiretroviral treatment)
  • DLCO > 80%
  • No pulmonary symptoms ≥ grade 2
  • No symptomatic pulmonary disease requiring medication including any of the following:
  • Dyspnea on or off exertion
  • Paroxysmal nocturnal dyspnea
  • Significant pulmonary disease (e.g., chronic obstruction/restrictive pulmonary disease)
  • No oxygen requirement
  • No home oxygen that meets the medicare requirement
  • No history of pulmonary toxicity after treatment with anthracyclines (e.g., doxorubicin hydrochloride, daunorubicin hydrochloride, mitoxantrone hydrochloride, bleomycin, or carmustine
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No psychosis
  • No other serious underlying medical condition that would preclude study participation
  • No prior allogeneic or autologous bone marrow transplantation
  • No concurrent immunotherapy
  • No concurrent biologic agents
  • No concurrent gene therapy
  • See Disease Characteristics
  • Recovered from prior chemotherapy
  • At least 48 hours since prior hydroxyurea for prevention of leukostasis
  • No other concurrent chemotherapy
  • At least 48 hours since prior glucocorticoids for prevention of leukostasis
  • No prior radiotherapy that included the heart in the field (e.g., mantle) or chest
  • No concurrent radiotherapy
  • No concurrent drugs that may cause QTc prolongation
  • No concurrent participation in another clinical trial involving a pharmacologic agent for symptom control or therapeutic intent
  • No other concurrent investigational drugs or therapy

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Scott KaufmannPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00098423
ClinicalTrials.gov processed this data on October 20, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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