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Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1NCT00275080

Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

A Phase 1 study testing vorinostat and decitabine 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 4 sites in Canada.

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 vorinostat when given together with decitabine in treating patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vorinostat and decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
4 sitesCanada
Study dates
Feb 2006to Aug 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 1 of the following:
  • Confirmed relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia in blast crisis (CML-BC)
  • Patients with acute promyelocytic leukemia who have relapsed while on tretinoin allowed
  • Patients with previously untreated AML who refuse induction chemotherapy allowed
  • Patients who are not candidates for aggressive management (those that have medical conditions that prevent the administration of standard curative chemotherapy or those who require an allogeneic bone marrow transplantation for curative therapy but lack an appropriate donor) are allowed
  • Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma (NHL)
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  • Histologically confirmed solid tumor that is metastatic or unresectable or for which standard curative or palliative measures do not exist or are no longer effective
  • Clinically or radiologically documented disease
  • Patients whose only evidence of disease is tumor marker elevation are not eligible
  • Patients with AML, ALL, or CML-BC who have cerebral spinal fluid involvement may be included
  • May be treated with intrathecal cytarabine and/or methotrexate prior to and/or during the study
  • No known brain metastases in patients with solid tumors or NHL
  • ECOG performance status 0-2
  • Karnofsky 60-100%
  • Life expectancy > 12 weeks for patients with solid tumors (including non-Hodgkin's lymphoma) and 6 weeks for patients with hematological malignancies
  • Patients with solid tumors (including NHL) must also have normal marrow function as defined below:
  • Leukocytes ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelets ≥ 100,000/mm^3
  • Creatinine ≤ 150 μmol/L
  • Creatinine clearance ≥ 60 mL/min
  • Bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal (ULN)
  • Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control or abstinence) prior to study entry and for the duration of study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in study
  • Able to take oral medications
  • Patients who have a clinical or radiological diagnosis of bowel obstruction are ineligible
  • No ongoing or active infection
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No psychiatric illness/social situations that would limit compliance with study requirements
  • No other uncontrolled intercurrent illness
  • No limitation on the number or types of prior therapy
  • At least 3 weeks since prior radiotherapy, chemotherapy (6 weeks for nitrosoureas or mitomycin C), or molecularly targeted agents
  • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
  • At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
  • Must have recovered from prior therapy
  • Patients with hematological malignancies may receive hydroxyurea until 24 hours prior to starting study medications
  • Previous surgery is permitted provided that wound healing has occurred
  • No prior decitabine
  • No other concurrent investigational agents
  • No other concurrent investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
  • No HIV-positive patients receiving combination antiretroviral therapy
  • No concurrent prophylactic hematopoietic growth factors (e.g. filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
  • Hematopoietic growth factors colony stimulating factors for the treatment of cytopenia may be permitted at the discretion of the principal investigator

Who cannot join

None listed.

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • Chedoke-McMaster Hospitals

    Hamilton, Ontario, L8S 4L8

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Princess Margaret Hospital Phase 2 Consortium

    Toronto, Ontario, M5G 2M9

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 1 Study of Vorinostat (Suberoylanilide Hydroxamic Acid; SAHA) in Combination With Decitabine in Patients With Advanced Solid Tumors, Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia in Blast Crisis

This phase I trial is studying the side effects and best dose of vorinostat when given together with decitabine in treating patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia.

Vorinostat 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 vorinostat together with decitabine may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Establish the maximum tolerated dose and recommended phase II dose of vorinostat in conjunction with decitabine in patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia in blast crisis.

SECONDARY OBJECTIVES:

  1. Identify the minimal effective dose of vorinostat in conjunction with decitabine that will lead to DNA demethylation, histone acetylation, and gene reactivation with tolerable toxicity in these patients.

II. Determine the pharmacokinetic profiles of vorinostat and decitabine in these patients. Correlate pharmacokinetic profiles of vorinostat and decitabine with toxicity and biological activity in these patients.

III. Assess the antitumor activity of vorinostat and decitabine in these patients.

OUTLINE: This is a parallel group, multicenter, dose-escalation study of vorinostat. Patients are stratified according to disease (solid tumors or non-Hodgkin's lymphoma [NHL] vs hematological malignancies).

Patients receive 1 of 2 dosing regimens.

Regimen 1 (sequential dosing): Patients receive oral vorinostat two or three times daily on days 6-21 or days 6-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Regimen 2 (concurrent dosing): Patients receive oral vorinostat two or three times daily on days 1-21, days 1-14 (patients with hematological malignancies only), or two times daily on days 1-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5.

Courses repeat every 28 days or 21 days (patients with hematological malignancies only) in the absence of disease progression or unacceptable toxicity. In both groups, cohorts of 3-6 patients receive escalating doses of vorinostat 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. The dose level just below MTD would be declared the recommended phase II dose (RPTD). Up to 10 patients are treated at the RPTD. After completion of study treatment, patients are followed at 4 weeks.

Being tested
vorinostat, decitabine
Medical subject headings
Congenital Abnormalities, Blast Crisis, Lymphoma, B-Cell, Marginal Zone, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

What participants receive

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

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

  • decitabineDrug

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

    Given IV

Study groups in NCT00275080
Study groupRoleWhat they receive
Treatment (enzyme inhibitor, chemotherapy)ExperimentalRegimen 1 (sequential dosing): Patients receive oral vorinostat two or three times daily on days 6-21 or days 6-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen 2 (concurrent dosing): Patients receive oral vorinostat two or three times daily on days 1-21, days 1-14 (patients with hematological malignancies only), or two times daily on days 1-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5.
Receives: Drug: vorinostat; Drug: decitabine

What is being measured

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

  1. Maximum tolerated dose and recommended phase II dose of vorinostat and decitabine

    Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

    Measured: Course 1

Secondary outcomes (5)

  1. Minimal effective dose of vorinostat in combination with decitabine by bone marrow and/or peripheral blood (for leukemia)

    Measured: Baseline and between days 3-10

  2. Pharmacokinetics of vorinostat in conjunction with decitabine

    Measured by peripheral blood. Performed by high-performance liquid chromatography (HPLC). Estimated by taking the mean concentration one hour after administration per patient on days 1 and 5 and estimating the mean, median and range over all patients.

    Measured: Days 1-15

  3. Antitumor activity

    Measured by Response Evaluation Criteria In Solid Tumors (RECIST), NCI-international working group (IWG), and NCI criteria.

    Measured: Every 4 weeks for leukemia and every 8 weeks for solid tumors or NHL

  4. Methylation status of gene promoter regions and gene expression

    Measured by bone marrow and/or peripheral blood.

    Measured: Baseline and between days 3-10

  5. Altered response of leukemic cells to PPAr and RAR ligands

    Collected by bone marrow and/or peripheral blood (for leukemia)

    Measured: Baseline and between days 3-8

Timeline

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

  1. First posted11 Jan 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionNov 2009
  4. Study completionAug 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
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00275080
Sponsor's protocol ID
NCI-2009-00092
Other IDs
NCI-2009-00092, PMH-PHL-046, CDR0000456473, NCI-6869, PHL-046, 6869, U01CA132123
Status last verified
Jun 2014
First submitted
10 Jan 2006
Last updated
27 Aug 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vorinostat and decitabine 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 4 sites in Canada.

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 48 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 27 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. 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 and recommended phase II dose of vorinostat and decitabine (time frame: Course 1). 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 NCT00275080.

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 27 Aug 2014.

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