Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

NCT00895934 | Completed Phase 1 Results

• 6 other identifiers: NCI-2012-01147IR-6921CDR00006422132288.008297P30CA015704
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

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 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); Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-limiting Toxicity (Phase I)

  42 days

• Number of Participants With Dose-limiting Toxicity After the Vorinostat Dose

  Up to 3 years

Secondary Outcomes (2)

• Number of Participants With Complete Remission

  up to 3 years

• Disease Relapse

  up to 2 years

Study Arms (2)

Phase 1 - Dose Finding

EXPERIMENTAL

Varying schedules and dose levels of vorinostat, azacitidine and gemtuzumab ozogamicin. Includes cohorts 1-3.

Drug: vorinostat; Drug: gemtuzumab ozogamicin; Drug: azacitidine

Phase 2 - Treatment at Selected Dose

EXPERIMENTAL

Vorinostat 400 mg/day on days 1-9, azacitidine 75 mg/m2/day on days 1-7, gemtuzumab ozogamicin 3 mg/m2/day on days 4 and 8.

Drug: vorinostat; Drug: gemtuzumab ozogamicin; Drug: azacitidine

Interventions

vorinostat DRUG

Given orally

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

Phase 1 - Dose Finding; Phase 2 - Treatment at Selected Dose

gemtuzumab ozogamicin DRUG

Given intravenously (IV)

Also known as: Calicheamicin, CDP-771, CMA-676, Mylotarg

Phase 1 - Dose Finding; Phase 2 - Treatment at Selected Dose

azacitidine DRUG

Given IV or subcutaneously (SC)

Also known as: 5-AC, 5-azacytidine, azacytidine, Vidaza

Phase 1 - Dose Finding; Phase 2 - Treatment at Selected Dose

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior morphological diagnosis of acute myeloid leukemia (AML) other then acute promyelocytic leukemia (APL) according to the 2001 WHO criteria; patients with biphenotypic AML are eligible
• Need for first salvage chemotherapy for persistent or relapsing disease, defined by standard criteria, after at least one course of conventional chemotherapy
• A bone marrow biopsy is not required but should be obtained if the aspirate is dilute, hypocellular, or not aspirable; outside marrow exams performed within the stipulated time period are acceptable if the slides are reviewed at the study institution
• Flow cytometric analysis of the marrow aspirate per institutional practice guidelines
• Duration of first complete remission (CR1) \< 12 months (or primary resistant disease)
• Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) if relapse occurs 6-12 months post-transplant
• ECOG/WHO/Zubrod performance status of 0-3 within 14 days prior to registration
• Off any active therapy for AML except hydroxyurea for at least 14 days prior to study registration, with resolution of all grade 3 and 4 non-hematological toxicities
• Willingness to discontinue taking any medications known to cause a risk of Torsades de Pointes
• Bilirubin =\< 1.5 x Institutional Upper Limit of Normal (IULN) unless elevation is due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (within 7 days prior to registration)
• SGOT (AST) and SGPT (ALT) =\< 1.5 x IULN unless elevation is due to hepatic infiltration by AML (within 7 days prior to registration)
• Serum creatinine =\< 1.5 x IULN (within 7 days prior to registration)
• No clinical or radiographical evidence of heart failure
• white blood cell (WBC) \< 25,000/uL within 3 days prior to registration
• Patients with symptoms/signs of hyperleukocytosis or WBC \> 100,000/uL can be treated with leukapheresis prior to enrollment

You may not qualify if:

• Remission or second or later relapse
• Diagnosis of another malignancy, unless diagnosed at least 2 years earlier and disease-free for at least 6 months after completion of curative intent therapy except:
• Treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, if definitive treatment has been completed
• Organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or a radical prostatectomy was performed
• Refractory/relapsing blast crisis of chronic myeloid leukemia (CML)
• Prior anti-AML treatment with GO, histone deacetylase (HDAC) inhibitor (including the use of valproic acid for control of seizure activity or other purposes), or demethylating agent
• Known hypersensitivity to GO, vorinostat, azacitidine, or mannitol
• Possible central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms no leukemic blasts in the cerebralspinal fluid (CSF)
• HIV-positive patients with cluster of differentiation (CD)4 count is \< 200 cells/uL or if AIDS-related complications
• Pregnancy; breastfeeding should be discontinued if the mother is treated with vorinostat, azacitidine, and GO
• Uncontrolled systemic infection, despite appropriate antibiotics or other treatment)
• Receipt of any other investigational agents

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

Harrison HealthPartners Hematology and Oncology-Bremerton

Bremerton, Washington, 98310, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Walter RB, Medeiros BC, Gardner KM, Orlowski KF, Gallegos L, Scott BL, Hendrie PC, Estey EH. Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study. Haematologica. 2014 Jan;99(1):54-9. doi: 10.3324/haematol.2013.096545. Epub 2013 Oct 18.

  PMID: 24142996 DERIVED

MeSH Terms

Conditions

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

Interventions

Vorinostat; Gemtuzumab; Calicheamicins; Azacitidine

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Enediynes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Diynes; Polyynes; Alkynes; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

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

rwalter@fhcrc.org

206-667-3599

Study Officials

• Roland Walter

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2009
• First Posted: May 8, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: May 23, 2019
• Results First Posted: February 6, 2015

Record last verified: 2019-05

Locations

US (4)