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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT00098423

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

A Phase 1 study testing tanespimycin and cytarabine in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Basophilic Leukemia, run by National Cancer Institute (NCI) 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

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tanespimycin and cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
Nov 2004to May 2009
Phase
Phase 1
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 73Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I And Pharmacological Trial Of 17-Allylamino -17-demethoxygeldanamycin (17-AAG) And Cytarabine In Refractory Leukemia And Myelodysplastic Syndrome

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.

Read the detailed description

OBJECTIVES:

  1. 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.

  1. 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.

Being tested
tanespimycin, cytarabine
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute

What participants receive

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

  • tanespimycinDrug

    Also called 17-AAG

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV

Study groups in NCT00098423
Study groupRoleWhat they receive
Treatment (chemotherapy)ExperimentalPatients receive induction therapy comprising cytarabine IV continuously on days 1-5 and tanespimycin IV over 1 hour on days 3 and 6. Patients achieving a morphologic complete response with 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 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 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.
Receives: Drug: tanespimycin; Drug: cytarabine

What is being measured

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

  1. Tolerability of tanespimycin 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

    Evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 standard toxicity grading.

    Measured: Day 21

Secondary outcomes (3)

  1. Clinical response

    Evaluated as suggested by the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Summarized by simple descriptive summary statistics across all patients in each group as well as by dose level. Possible relationships between response and dose level will be explored graphically.

    Measured: Every 2 weeks

  2. Plasma level of tanespimycin

    Summarized by simple descriptive summary statistics across all patients in each group as well as by dose level. Possible relationships between pharmacokinetic (PK) parameters and p450 3A5 genotypes will be explored.

    Measured: Day 3

  3. Effects on client proteins

    Analyzed by immunoblotting. Results will be displayed graphically and analyzed using simple descriptive statistics.

    Measured: Days 1, 3, and 4 of course 1

Timeline

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

  1. First posted8 Dec 2004 (estimated)
  2. Study startNov 2004
  3. Primary completionMay 2009

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098423
Sponsor's protocol ID
NCI-2009-00056
Other IDs
NCI-2009-00056, NCI-6383, CDR0000401509, MC0313, 6383, U01CA070095, U01CA069912
Status last verified
Sep 2013
First submitted
7 Dec 2004
Last updated
30 Sep 2013
Results posted
No

Publications

  • Kaufmann SH, Karp JE, Litzow MR, Mesa RA, Hogan W, Steensma DP, Flatten KS, Loegering DA, Schneider PA, Peterson KL, Maurer MJ, Smith BD, Greer J, Chen Y, Reid JM, Ivy SP, Ames MM, Adjei AA, Erlichman C, Karnitz LM. Phase I and pharmacological study of cytarabine and tanespimycin in relapsed and refractory acute leukemia. Haematologica. 2011 Nov;96(11):1619-26. doi: 10.3324/haematol.2011.049551. Epub 2011 Jul 26.

    PubMed 21791475

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tanespimycin and cytarabine in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Basophilic Leukemia, run by National Cancer Institute (NCI) 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 73 inclusion and 0 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 30 Sep 2013. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Tolerability of tanespimycin 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 (time frame: Day 21). 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 NCT00098423, which also lists 1 linked publication.

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 30 Sep 2013.

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