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Adult Acute Megakaryoblastic Leukemia (M7)Phase 1/2NCT00895934

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

A Phase 1/2 study testing vorinostat, gemtuzumab ozogamicin and azacitidine in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by National Cancer Institute (NCI) at 4 sites 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

The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia… Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
vorinostat, gemtuzumab ozogamicin and azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
4 sitesUnited States
Study dates
May 2009to Sep 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Who may be able to join

  • Prior morphological diagnosis of acute myeloid leukemia (AML) other then acute promyelocytic leukemia (APL) according to the 2001 WHO criteria; patients with biphenotypic AML are eligible
  • Need for first salvage chemotherapy for persistent or relapsing disease, defined by standard criteria, after at least one course of conventional chemotherapy
  • A bone marrow biopsy is not required but should be obtained if the aspirate is dilute, hypocellular, or not aspirable; outside marrow exams performed within the stipulated time period are acceptable if the slides are reviewed at the study institution
  • Flow cytometric analysis of the marrow aspirate per institutional practice guidelines
  • Duration of first complete remission (CR1) < 12 months (or primary resistant disease)
  • Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) if relapse occurs 6-12 months post-transplant
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  • ECOG/WHO/Zubrod performance status of 0-3 within 14 days prior to registration
  • Off any active therapy for AML except hydroxyurea for at least 14 days prior to study registration, with resolution of all grade 3 and 4 non-hematological toxicities
  • Willingness to discontinue taking any medications known to cause a risk of Torsades de Pointes
  • Bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN) unless elevation is due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (within 7 days prior to registration)
  • SGOT (AST) and SGPT (ALT) =< 1.5 x IULN unless elevation is due to hepatic infiltration by AML (within 7 days prior to registration)
  • Serum creatinine =< 1.5 x IULN (within 7 days prior to registration)
  • No clinical or radiographical evidence of heart failure
  • white blood cell (WBC) < 25,000/uL within 3 days prior to registration
  • Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/uL can be treated with leukapheresis prior to enrollment
  • Collection of bone marrow and peripheral blood specimens for correlative studies prior to study treatment is highly recommended; peripheral blood only is acceptable if the peripheral blast count is > 5,000/uL and > 50% of total WBC
  • Must agree to use adequate contraception prior to and during the study
  • Can understand and sign a written informed consent document; a legally authorized representative can provide consent if the patient is unable

Who cannot join

  • Remission or second or later relapse
  • Diagnosis of another malignancy, unless diagnosed at least 2 years earlier and disease-free for at least 6 months after completion of curative intent therapy except:
  • Treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, if definitive treatment has been completed
  • Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or a radical prostatectomy was performed
  • Refractory/relapsing blast crisis of chronic myeloid leukemia (CML)
  • Prior anti-AML treatment with GO, histone deacetylase (HDAC) inhibitor (including the use of valproic acid for control of seizure activity or other purposes), or demethylating agent
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  • Known hypersensitivity to GO, vorinostat, azacitidine, or mannitol
  • Possible central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms no leukemic blasts in the cerebralspinal fluid (CSF)
  • HIV-positive patients with cluster of differentiation (CD)4 count is < 200 cells/uL or if AIDS-related complications
  • Pregnancy; breastfeeding should be discontinued if the mother is treated with vorinostat, azacitidine, and GO
  • Uncontrolled systemic infection, despite appropriate antibiotics or other treatment)
  • Receipt of any other investigational agents

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Harrison HealthPartners Hematology and Oncology-Bremerton

    Bremerton, Washington, 98310

  • Fred Hutchinson Cancer Research Center

    Seattle, Washington, 98109

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Stanford University Hospitals and Clinics

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Vorinostat (Zolinza®) in Combination With Gemtuzumab Ozogamicin (Mylotarg®) and Azacitidine (Vidaza®) in Patients 50 Years of Age and Older With Relapsed/Refractory Non-APL Acute Myeloid Leukemia (AML)

The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the vorinostat dose with the most favorable efficacy and toxicity when combined with azacitidine and GO.

SECONDARY OBJECTIVES:

  1. Describe the complete response (CR)/ CR with inadequate recovery (CRi) rate after a total of 6 cycles of therapy.

II. Describe the disease-free survival of patients that achieve CR/CRi. III. Determine whether acute myeloid leukemia (AML) characteristics associated with preclinical GO efficacy predict for clinical benefit, and assess whether differentiation-inducing agents modulate these characteristics and lower the apoptotic threshold for calicheamicin-gamma1-induced cytotoxicity (in vitro correlative and mechanistic studies).

OUTLINE: This is phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) on days 1-9, azacitidine subcutaneously (SC) or intravenously (IV) over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 4 and 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Being tested
vorinostat, gemtuzumab ozogamicin, azacitidine
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

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

  • gemtuzumab ozogamicinDrug

    Also called Calicheamicin, CDP-771, CMA-676, Mylotarg

    Given intravenously (IV)

  • azacitidineDrug

    Also called 5-AC, 5-azacytidine, azacytidine, Vidaza

    Given IV or subcutaneously (SC)

Study groups in NCT00895934
Study groupRoleWhat they receive
Phase 1 - Dose FindingExperimentalVarying schedules and dose levels of vorinostat, azacitidine and gemtuzumab ozogamicin. Includes cohorts 1-3.
Receives: Drug: vorinostat; Drug: gemtuzumab ozogamicin; Drug: azacitidine
Phase 2 - Treatment at Selected DoseExperimentalVorinostat 400 mg/day on days 1-9, azacitidine 75 mg/m2/day on days 1-7, gemtuzumab ozogamicin 3 mg/m2/day on days 4 and 8.
Receives: Drug: vorinostat; Drug: gemtuzumab ozogamicin; Drug: azacitidine

What is being measured

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

  1. Number of Participants With Dose-limiting Toxicity (Phase I)

    Measured: 42 days

  2. Number of Participants With Dose-limiting Toxicity After the Vorinostat Dose

    Measured: Up to 3 years

Secondary outcomes (2)

  1. Number of Participants With Complete Remission

    Efficacy Defined as Best Response Achieved During Study Treatment Measured by Complete Remission (CR) Rate

    Measured: up to 3 years

  2. Disease Relapse

    Measured: up to 2 years

Timeline

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

  1. First posted8 May 2009 (estimated)
  2. Study startMay 2009
  3. Primary completionJul 2013
  4. Study completionSep 2013

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00895934
Sponsor's protocol ID
NCI-2012-01147
Other IDs
NCI-2012-01147, IR-6921, CDR0000642213, 2288.00, 8297, P30CA015704
Status last verified
May 2019
First submitted
7 May 2009
Last updated
23 May 2019
Data monitoring committee
No

Publications

  • Walter RB, Medeiros BC, Gardner KM, Orlowski KF, Gallegos L, Scott BL, Hendrie PC, Estey EH. Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study. Haematologica. 2014 Jan;99(1):54-9. doi: 10.3324/haematol.2013.096545. Epub 2013 Oct 18.

    PubMed 24142996

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing vorinostat, gemtuzumab ozogamicin and azacitidine in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by National Cancer Institute (NCI) at 4 sites 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 18 inclusion and 12 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 23 May 2019. 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 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Dose-limiting Toxicity (Phase I) (time frame: 42 days). The study lists 2 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 NCT00895934, 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 23 May 2019.

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