Vorinostat and Gemtuzumab in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: gemtuzumab ozogamicin (Drug); vorinostat (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Fred Hutchinson Cancer Research Center Official(s) and/or principal investigator(s):
Roland Walter, MD, PhD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Summary
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes
needed for cell growth. Monoclonal antibodies, such as gemtuzumab, can block cancer growth
in different ways. Some block the ability of cancer cells to grow and spread. Others find
cancer cells and help kill them or carry cancer-killing substances to them. Giving
vorinostat together with gemtuzumab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving vorinostat together with gemtuzumab
works in treating older patients with previously untreated acute myeloid leukemia.
Clinical Details
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
Study design: Treatment, Non-Randomized, Open Label
Primary outcome: Complete remission (CR) or CR with incomplete blood count recovery (CRi) rate (Good risk group)30-day survival (Poor risk group)
Secondary outcome: 30-day survival (Good risk group)CR/CRi rate (Poor risk group) Frequency and severity of regimen-associated toxicities Relapse-free survival
Detailed description:
OBJECTIVES:
Primary
- Determine the complete remission (CR)/CR with incomplete blood count recovery (CRi)
rate in older patients with previously untreated acute myeloid leukemia (AML) treated
with vorinostat and gemtuzumab ozogamicin. (Good risk group)
- Determine the 30-day survival of patients treated with this regimen. (Poor risk group)
Secondary
- Estimate the 30-day survival of patients treated with this regimen. (Good risk group)
- Determine the CR/CRi rate in patients treated with this regimen. (Poor risk group)
- Estimate the frequency and severity of regimen-associated toxicities in these patients.
- Investigate the relapse-free survival of patients who achieve CR/CRi and receive
maintenance therapy on this study.
- Define cellular factors associated with clinical response to this treatment regimen and
determine the mechanisms underlying the synergistic effect between gemtuzumab
ozogamicin and vorinostat on primary AML cells (in vitro correlative and mechanistic
studies).
OUTLINE: This is a multicenter study. Patients are stratified according to risk status (good
risk [60-69 years of age OR ECOG/WHO/ZUBROD performance status (PS) 0-1] vs poor risk [≥ 70
years of age AND ECOG/WHO/ZUBROD PS 2-3]).
- Remission induction therapy: Patients receive oral vorinostat once daily on days 1-9
and gemtuzumab ozogamicin IV over 2 hours on day 8. Patients achieving a complete
remission (CR) or CR with incomplete blood count recovery (CRi) proceed to
consolidation therapy. Patients with residual leukemia (≥ 5% blasts) and no
hypocellularity receive a second course of induction therapy beginning between days
15-22. Patients achieving a CR or CRi after the third course proceed to consolidation
therapy. Patients with continued persistent disease (≥ 5% blasts) are removed from the
study.
- 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 in the absence of disease progression or
unacceptable toxicity. Patients who remain in CR or CRi proceed to maintenance therapy.
- Maintenance therapy: Patients receive oral vorinostat once daily on days 1-14.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
Eligibility
Minimum age: 60 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Morphological diagnosis of acute myeloid leukemia (AML)
- No acute promyelocytic leukemia (FAB M3)
- Must have cytogenetic analysis performed on bone marrow specimen
- 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/or peripheral blood specimens available
- Previously untreated disease
- Patients with a history of antecedent myelodysplastic syndrome (MDS) are eligible, if
prior treatment did not include intensive chemotherapy AND patients are off therapy
for ≥ 30 days prior to study registration and recovered
- Prior hematopoietic growth factors, thalidomide/lenalidomide,
azacitidine/decitabine, arsenic trioxide, signal transduction inhibitors, or
low-dose cytarabine (< 100 mg/m2/day) for treatment of MDS allowed
- No myeloid blast crisis of chronic myelogenous leukemia
- No clinical evidence suggestive of CNS involvement with leukemia unless a lumbar
puncture confirms the absence of leukemic blasts in the cerebrospinal fluid
PATIENT CHARACTERISTICS:
- ECOG/WHO/Zubrod performance status 0-3
- WBC < 10,000/μL
- Patients with WBC ≥10,000/μL must undergo cytoreduction with hydroxyurea prior
to study enrollment
- Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/μL may be
treated with leukapheresis prior to study enrollment
- Bilirubin ≤ 2. 5 times upper limit of normal (ULN) (unless elevation is thought to be
due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis)
- ALT and AST ≤ 1. 5 times ULN (unless elevation is thought to be due to hepatic
infiltration by AML)
- Serum creatinine ≤ 1. 5 times ULN
- Not pregnant or nursing
- For women: postmenopausal status or negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study therapy
- LVEF ≥ 40% by MUGA scan or echocardiogram
- No clinical evidence of congestive heart failure
- No other malignancy unless the patient was diagnosed ≥ 2 years ago AND has been
disease-free for ≥ 6 months following completion of curative intent therapy
- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia are eligible provided definitive treatment for the
condition has been completed
- Patients with organ-confined prostate cancer are eligible provided there is no
evidence of recurrent or progressive disease, based on prostate-specific antigen
(PSA) values, AND hormonal therapy has been initiated or a radical prostatectomy
has been performed
- No known hypersensitivity to hydroxyurea, gemtuzumab ozogamicin, or vorinostat
- No HIV positivity
- No uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection AND infection has not
improved despite appropriate antibiotics or other treatment)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior systemic chemotherapy for AML, except for hydroxyurea
- No prior treatment with AML induction-type chemotherapy, gemtuzumab ozogamicin, or
high-dose chemotherapy with hematopoietic stem cell support
- More than 3 years since prior treatment with histone deacetylase inhibitors (HDACi),
including the use of valproic acid for seizure activity or other purposes
- Must not plan to undergo treatment for prior malignancy
- No concurrent hormone therapy
Locations and Contacts
Stanford Cancer Center, Stanford, California 94305-5824, United States; Recruiting
Clinical Trials Office - Stanford Cancer Center, Phone: 650-498-7061, Email: cctoffice@stanford.edu
Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States; Recruiting
Clinical Trials Office - Robert H. Lurie Comprehensive Cancer, Phone: 312-695-1301, Email: cancer@northwestern.edu
Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States; Recruiting
Clinical Trials Office - Barbara Ann Karmanos Cancer Institute, Phone: 313-576-9363
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States; Recruiting
Clinical Trials Office - Wake Forest University Comprehensive, Phone: 336-713-6771
M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Clinical Trials Office - M. D. Anderson Cancer Center at the U, Phone: 713-792-3245
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109-1024, United States; Recruiting
Roland Walter, MD, PhD, Phone: 800-804-8824
Seattle Cancer Care Alliance, Seattle, Washington 98109-1023, United States; Recruiting
Clinical Trials Office - Seattle Cancer Care Alliance, Phone: 800-804-8824
Veterans Affairs Medical Center - Seattle, Seattle, Washington 98108, United States; Recruiting
William H. Schubach, MD, Phone: 206-764-2265
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: March 2008
Last updated: July 7, 2009
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