Vorinostat and Gemtuzumab in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00673153

Purpose

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.

Condition	Intervention	Phase
Leukemia	Drug: gemtuzumab ozogamicin Drug: vorinostat	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Gemtuzumab ozogamicin Suberoylanilide hydroxamic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete remission (CR) or CR with incomplete blood count recovery (CRi) rate (Good risk group) [ Designated as safety issue: No ]
30-day survival (Poor risk group) [ Designated as safety issue: No ]

Secondary Outcome Measures:

30-day survival (Good risk group) [ Designated as safety issue: No ]
CR/CRi rate (Poor risk group) [ Designated as safety issue: No ]
Frequency and severity of regimen-associated toxicities [ Designated as safety issue: Yes ]
Relapse-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	107
Study Start Date:	September 2008
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

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 second 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 every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 1 year.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Morphological diagnosis of acute myeloid leukemia (AML)
- No acute promyelocytic leukemia (FAB M3)
Previously untreated disease
Patients with a history of antecedent myelodysplastic syndrome are eligible, if prior treatment did not include intensive chemotherapy AND patients are off therapy for ≥ 30 days prior to study registration
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%
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673153

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Roland Walter, MD, MPH 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Roland Walter, MD, MPH

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Fred Hutchinson Cancer Research Center ( Roland Walter )
Study ID Numbers:	CDR0000595176, FHCRC-2200.00, IR-6688, MERCK-FHCRC-2200.00
Study First Received:	May 6, 2008
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00673153
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)

adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
untreated adult acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)
secondary acute myeloid leukemia

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Vorinostat
Acute myelogenous leukemia
Acute myelomonocytic leukemia
Leukemia, Myeloid
Gemtuzumab
Leukemia, Myeloid, Acute
Di Guglielmo's syndrome
Antibodies, Monoclonal
Leukemia, Myelomonocytic, Acute

Leukemia
Antibodies
Leukemia, Erythroblastic, Acute
Neoplasm Metastasis
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute monoblastic leukemia
Acute myelocytic leukemia
Immunoglobulins

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions

Neoplasms
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009