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Trial record 15 of 200 for:    "Acute monoblastic leukemia"

Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

This study has been terminated.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00673153
First received: May 6, 2008
Last updated: November 3, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
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 Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Untreated Adult Acute Myeloid Leukemia
Drug: gemtuzumab ozogamicin
Drug: vorinostat
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Probability of achieving CR or CRi with induction therapy (Good-risk group) [ Time Frame: After completion of induction therapy ] [ Designated as safety issue: No ]
  • Probability of survival (Poor-risk group) [ Time Frame: At day 30 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relapse-free survival (Good- and Poor-risk group) [ Time Frame: At relapse ] [ Designated as safety issue: No ]
  • Probability of achieving CR or CRi with induction therapy (Poor-risk group) [ Time Frame: After completion of induction therapy ] [ Designated as safety issue: No ]
  • Probability of survival (Good-risk group) [ Time Frame: At day 30 ] [ Designated as safety issue: No ]

Estimated Enrollment: 107
Study Start Date: March 2008
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

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.

Drug: gemtuzumab ozogamicin
Given IV
Other Names:
  • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
  • CDP-771
  • CMA-676
  • hP67.6-Calicheamicin
  • Mylotarg
  • WAY-CMA-676
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Roland Walter Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided by Fred Hutchinson Cancer Research Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Walter, Roland, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00673153     History of Changes
Other Study ID Numbers: 2200.00, NCI-2010-00401
Study First Received: May 6, 2008
Last Updated: November 3, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Bone Marrow Diseases
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Gemtuzumab
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014