Brief Title
Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Official Title
Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid or SAHA; Zolinza™) in Combination With Gemtuzumab Ozogamicin (Mylotarg™) as Induction and Post-Remission Therapy in Older Patients With Previously Untreated Non-M3 Acute Myeloid Leukemia
Brief Summary
RATIONALE: Vorinostat may stop the growth of cancer cells by interfering with various
proteins needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin (GO),
can block cancer growth in different ways. GO finds cancer cells and helps kill them by
carrying a cancer-killing substance to them. Giving vorinostat together with gemtuzumab
ozogamicin may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving vorinostat together with gemtuzumab
ozogamicin works in treating older patients with previously untreated acute myeloid leukemia.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the CR/CRi rate after treatment with vorinostat plus GO. (Good risk group)
II. To determine the 30-day survival after treatment with vorinostat plus GO. (Poor risk
group)
SECONDARY OBJECTIVES:
I. To estimate the frequency and severity of regimen-associated toxicities, along with 30-day
survival after start of treatment with vorinostat plus GO. (Good risk group) II. To determine
the CR/CRi rate after treatment with vorinostat plus GO, and estimate the frequency and
severity of regimen-associated toxicities. (Poor risk group) III. To investigate the
relapse-free survival of patients who achieve CR/CRi and receive maintenance therapy on this
study.
IV. To define cellular factors associated with clinical response to GO/vorinostat and
determine the mechanisms underlying the synergistic effect between GO and vorinostat on
primary AML cells (in vitro correlative and mechanistic studies).
OUTLINE:
REMISSION INDUCTION THERAPY: Patients receive oral vorinostat once daily on days 1-9 and
gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 15-22 days for up to
3 courses.
CONSOLIDATION THERAPY: Beginning within 60 days after the completion of remission induction
therapy, patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV
over 2 hours on day 8.
MAINTENANCE THERAPY: Patients receive oral vorinostat once daily on days 1-14. Treatment
repeats every 28 days for 4 courses.
All treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 3
years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants Achieving CR or CRi With Induction Therapy (Good-risk Group)
Secondary Outcome
Relapse-free Survival (Good- and Poor-risk Group)
Condition
Adult Acute Megakaryoblastic Leukemia (M7)
Intervention
gemtuzumab ozogamicin
Study Arms / Comparison Groups
Arm I
Description: REMISSION INDUCTION THERAPY: Patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 15-22 days for up to 3 courses. . CONSOLIDATION THERAPY: Beginning within 60 days after the completion of remission induction therapy, patients receive oral vorinostat once daily on days 1-9 and gemtuzumab ozogamicin IV over 2 hours on day 8. MAINTENANCE THERAPY: Patients receive oral vorinostat once daily on days 1-14. Treatment repeats every 28 days for 4 courses.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
31
Start Date
March 2008
Primary Completion Date
August 2010
Eligibility Criteria
Inclusion Criteria:
- Morphological diagnosis of AML other then acute promyelocytic leukemia (FAB M3)
according to WHO diagnostic criteria; diagnosis of AML must be based on bone marrow or
peripheral blood studies obtained within 28 days prior to study registration or start
of hydroxyurea (for patients presenting with WBC >= 10,000/uL), and no potentially
anti-leukemic therapy (with the exception of hydroxyurea) must have been given between
AML diagnosis and study registration; a bone marrow biopsy is not routinely required
but should be obtained if the aspirate is dilute, hypocellular, or inaspirable;
outside bone marrows performed within the stipulated time period are acceptable as
long as the slides are reviewed at a study institution
- Cytogenetic analysis on bone marrow or peripheral blood specimen is available; based
on the result from the first interim analysis, patients stratified into the good-risk
group are only eligible if their AML has favorable cytogenetics (core-binding factor
AML) or has a normal karyotype; patients stratified into the poor-risk group are
eligible independent of the cytogenetic analysis
- Pretreatment bone marrow and peripheral blood specimens for correlative studies are
available; if bone marrow was performed at an outside facility, submission of
peripheral blood only is acceptable as long as the peripheral blast count is >
5,000/uL and > 50% of total WBC
- Patients with a history of antecedent MDS are eligible, if prior treatment did not
include intensive chemotherapy; patients may have received hematopoietic growth
factors, thalidomide/lenalidomide, 5-azacytidine/decitabine, arsenic trioxide, signal
transduction inhibitors, or low dose cytarabine (< 100 mg/m2/day) for treatment of
MDS; patients must be off prior therapy for MDS at least 30 days prior to study
registration, and all non-hematologic toxicities must have resolved to < grade 2
- ECOG/WHO/Zubrod performance status of 0-3
- Bilirubin =< 2.5 x Institutional Upper Limit of Normal (IULN) unless elevation is
thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
(assessed within 14 days prior to registration)
- SGOT (AST) and SPGT (ALT) =< 1.5 x IULN unless elevation is thought to be due to
hepatic infiltration by AML (assessed within 14 days prior to registration)
- Serum creatinine =< 1.5 x IULN (assessed within 14 days prior to registration)
- Left ventricular ejection fraction >= 40% and no clinical evidence of congestive heart
failure (assessed within 28 days prior to registration, e.g. by MUGA scan or
echocardiography)
- Men of reproductive potential must use an effective contraceptive method throughout
the study and for a period of at least 3 months after the study
- Women must be postmenopausal; a postmenopausal woman is defined as a woman who has
experienced amenorrhea > 12 consecutive months or a woman on hormone replacement
therapy with documented FSH level > 35 mIU/mL (women of childbearing potential must
have a pregnancy test within 28 days prior to registration, and must use an adequate
method of contraception to avoid pregnancy throughout the study and for a period of at
least 3 months after the study)
- Provide signed written informed consent
- Willingness to undergo bone marrow examination on day 8 of first induction cycle
- WBC < 10,000/uL (patients with WBC >= 10,000/uL must undergo cytoreduction with
hydroxyurea prior to enrollment and will not be enrolled if the WBC remains >=
10,000/uL (of note, patients with symptoms/signs of hyperleukocytosis or WBC >
100,000/uL can be treated with leukapheresis prior to enrollment)
Exclusion Criteria:
- Diagnosis of another malignancy, unless the patient was diagnosed at least 2 years
earlier and has been disease-free for at least 6 months following the completion of
curative intent therapy; there should be no plan to begin therapy for the prior
malignancy at the time of study registration; prior treatment with AML induction-type
chemotherapy is not allowed (note the following exceptions: patients with treated
non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia,
regardless of the disease-free duration, are eligible for this study if definitive
treatment for the condition has been completed; patients with organ-confined prostate
cancer with no evidence of recurrent or progressive disease based on prostate-specific
antigen [PSA] values are also eligible for this study if hormonal therapy has been
initiated or a radical prostatectomy has been performed; concurrent hormonal therapy
is allowed)
- Myeloid blast crisis of chronic myelogenous leukemia (CML)
- Prior systemic chemotherapy for AML with the exception of hydroxyurea
- Prior treatment with AML induction-type chemotherapy, GO, HDAC inhibitors, or high
dose chemotherapy with hematopoietic stem cell support
- Treatment with HDAC inhibitors during the last 3 years prior to registration,
including the use of valproic acid for seizure activity or other purposes
- Known hypersensitivity to hydroxyurea, GO, or vorinostat
- Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia
unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal
fluid (CSF)
- Prior positive test for the human immunodeficiency virus (HIV)
- Breastfeeding
- Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment)
Gender
All
Ages
60 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Roland Walter, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00673153
Organization ID
2200.00
Secondary IDs
NCI-2010-00401
Responsible Party
Principal Investigator
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Roland Walter, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
May 2017