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Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1NCT00703300

Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

A Phase 1 study testing bortezomib, decitabine and pharmacological study in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), 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 bortezomib when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib, decitabine and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Jun 2008to Oct 2014
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 acute myeloid leukemia (AML), meeting one of the following criteria:
  • Relapsed or refractory disease (≥ 18 years of age)
  • Previously untreated disease (≥ 60 years of age)
  • Secondary AML or therapy-related AML allowed
  • No granulocytic sarcoma as the sole site of disease
  • No active or relapsed CNS disease
Show all 42Show fewer
  • No advanced malignant solid tumors
  • ECOG performance status 0-2
  • Life expectancy > 6 months (if patient has co-morbid illness)
  • Total bilirubin < 2.0 mg/dL
  • AST and ALT < 2.5 times upper limit of normal
  • Creatinine < 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with HIV infection are eligible provided the following criteria are met:
  • No history of AIDS
  • Has a sufficiently high CD4 count (> 400/mm³)
  • Has low HIV viral loads (< 30,000 copies/mL plasma)
  • Does not require anti-HIV therapy
  • No uncontrolled active infection
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to decitabine or bortezomib that are not easily managed
  • No hypersensitivity to boron or mannitol
  • No concurrent uncontrolled illness including, but not limited to, any of the following:
  • Symptomatic congestive heart failure
  • Unstable or uncontrolled angina pectoris
  • Serious cardiac arrhythmia
  • Myocardial infarction within the past 6 months
  • New York Heart Association class III-IV heart failure
  • Severe uncontrolled ventricular arrhythmias
  • Acute ischemia or active conduction system abnormalities by ECG
  • No serious medical or psychiatric illness or social situation that would preclude participation in this study
  • No pre-existing neuropathy ≥ grade 2
  • No other serious neurologic toxicity that would significantly increase the risk of complications from bortezomib therapy
  • Recovered from prior therapy (toxicity < grade 2)
  • More than 14 days since prior investigational agents
  • More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
  • Prior decitabine or azacitidine for myelodysplastic syndromes (MDS) or AML allowed
  • More than 6 months since prior decitabine, azacitidine, or bortezomib
  • No concurrent palliative radiotherapy
  • No other concurrent investigational agents
  • No other concurrent direct anti-leukemia therapy

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase I Study of Decitabine (Dacogen) and Bortezomib (Velcade) in Acute Myeloid Leukemia

This phase I trial is studying the side effects and best dose of bortezomib when given together with decitabine in treating patients with acute myeloid leukemia. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with decitabine may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of bortezomib (Velcade, PS-341) in combination with decitabine in patients with acute myeloid leukemia (AML) II. To define the specific toxicities and the dose limiting toxicity (DLT) of decitabine plus bortezomib combination

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (ORR). II. To determine the rate of complete remission (CR) of decitabine plus bortezomib in AML III. To correlate the biological activity of decitabine as demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of decitabine.

IV. To characterize the biological activity of bortezomib as a potential demethylating agent V. To correlate intracellular concentration of decitabine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response.

VI. To explore the biologic role of microRNAs in determining clinical response to the decitabine plus bortezomib combination and achievement of the other pharmacodynamic endpoints.

OUTLINE: This is a dose-escalation study of bortezomib.

Patients receive decitabine intravenously (IV) over 1 hour on days 1-5 or 1-10 and bortezomib IV on days 5 and 8 or days 5, 8, 12, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose is determined, an additional 6 patients are treated at the recommended phase II dose.

After completion of study treatment, patients are followed for at least 30 days.

Being tested
bortezomib, decitabine, pharmacological study, laboratory biomarker analysis
Medical subject headings
Congenital Abnormalities, Leukemia, Myeloid, Acute

What participants receive

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

  • bortezomibDrug

    Also called LDP 341, MLN341, VELCADE

    Given IV

  • decitabineDrug

    Also called 5-aza-dCyd, 5AZA, DAC

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Optional correlative studies

Study groups in NCT00703300
Study groupRoleWhat they receive
Treatment (enzyme inhibitor therapy and chemotherapy)ExperimentalPatients receive decitabine IV over 1 hour on days 1-5 or 1-10 and bortezomib IV on days 5 and 8 or days 5, 8, 12, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose is determined, an additional 6 patients are treated at the recommended phase II dose.
Receives: Drug: bortezomib; Drug: decitabine; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum-tolerated dose (MTD) of bortezomib in combination with decitabine

    If a patient meets the definition of dose-limiting toxicity (DLT), the patient may continue on with study therapy provided that the toxicity can be managed according to the dose modification guidelines. For DLT = 2, dose level will stop. This dose level will be declared the MTD administered dose (highest dose administered). As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

    Measured: During course 1 (28 days)

  2. Specific toxicities

    Toxicity will be characterized using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

    Measured: Up to 30 days post-treatment

  3. DLT of bortezomib in combination with decitabine

    Toxicity will be characterized using the National Cancer Institute CTCAE version 3.0. As an exploratory, phase I study, no inferential statistical tests of hypotheses are planned. Data collected will be descriptive and provide limited estimates of variability given the small sample sizes at each dose level.

    Measured: During course 1 (28 days)

Secondary outcomes (2)

  1. Overall response rate

    Assessment of clinical response will be made according to International Working Group criteria. The major criteria for judging response will include physical examination and examination of blood and bone marrow.

    Measured: Up to 30 days post-treatment

  2. Rate of complete remission (CR)

    The major criteria for judging response will include physical examination and examination of blood and bone marrow (morphologic CR and cytogenetic CR)

    Measured: Up to 30 days post-treatment

Timeline

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

  1. First posted23 Jun 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionMar 2010
  4. Study completionOct 2014

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00703300
Sponsor's protocol ID
NCI-2009-00263
Other IDs
NCI-2009-00263, OSU-08047, 2008C0034, CDR0000598089, 08047, 8008, U01CA076576, P30CA016058
Status last verified
Sep 2014
First submitted
20 Jun 2008
Last updated
7 Nov 2014
Results posted
No

Publications

  • Blum W, Schwind S, Tarighat SS, Geyer S, Eisfeld AK, Whitman S, Walker A, Klisovic R, Byrd JC, Santhanam R, Wang H, Curfman JP, Devine SM, Jacob S, Garr C, Kefauver C, Perrotti D, Chan KK, Bloomfield CD, Caligiuri MA, Grever MR, Garzon R, Marcucci G. Clinical and pharmacodynamic activity of bortezomib and decitabine in acute myeloid leukemia. Blood. 2012 Jun 21;119(25):6025-31. doi: 10.1182/blood-2012-03-413898. Epub 2012 May 7.

    PubMed 22566605

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, decitabine and pharmacological study in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), 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 42 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 7 Nov 2014. 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?

Maximum-tolerated dose (MTD) of bortezomib in combination with decitabine (time frame: During course 1 (28 days)). The study lists 3 primary outcomes in all. 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 NCT00703300, 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 7 Nov 2014.

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