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

NCT00673153 | Terminated Phase 2 Results

• 2 other identifiers: 2200.00NCI-2010-00401
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants Achieving CR or CRi With Induction Therapy (Good-risk Group)

  after completion of induction therapy, administered every 21-42 days for up to two courses

• Number of Participants Alive at Day 30 (Poor-risk Group)

  At day 30

Secondary Outcomes (3)

• Relapse-free Survival (Good- and Poor-risk Group)

  At relapse

• Number of Participants Achieving CR or CRi With Induction Therapy (Poor-risk Group)

  after completion of induction therapy, administered every 21-42 days for up to two courses

• Number of Participants Alive at Day 30 (Good-risk Group)

  At day 30

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: vorinostat; Other: laboratory biomarker analysis

Interventions

gemtuzumab ozogamicin DRUG

Given IV

Also known as: Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody, CDP-771, CMA-676, hP67.6-Calicheamicin, Mylotarg, WAY-CMA-676

Arm I

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Stanford University

Stanford, California, 94305, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Walter RB, Medeiros BC, Powell BL, Schiffer CA, Appelbaum FR, Estey EH. Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia. Haematologica. 2012 May;97(5):739-42. doi: 10.3324/haematol.2011.055822. Epub 2011 Dec 1.

  PMID: 22133771 DERIVED

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

Gemtuzumab; Vorinostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Roland B. Walter, MD, PhD, MS
• Organization: Fred Hutch Cancer Research Center

(206) 667-3599

Study Officials

• Roland Walter

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: May 7, 2008
• Study Start: March 1, 2008
• Primary Completion: August 1, 2010
• Last Updated: June 1, 2017
• Results First Posted: June 1, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)