Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT00818649 | Terminated Phase 2 Results DMC

• 4 other identifiers: 2008LS044MT2008-06R0808M44081MILLENNIUM-X05269
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with vorinostat works in treating patients with high-risk myelodysplastic syndrome or acute myelogenous leukemia.

Conditions

Leukemia; Myelodysplastic Syndrome

Keywords

de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; refractory anemia with excess blasts; adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute minimally differentiated myeloid leukemia (M0); 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); recurrent adult acute myeloid leukemia; untreated adult acute myeloid leukemia; 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)

Outcome Measures

Primary Outcomes (1)

• Number of Patients by Best Clinical Response

  Assessed by the International Working Group response criteria: Complete Remission - \<5% myeloblasts with normal maturation of all cell lines; Partial Remission - bone marrow blasts decreased by \> 50% over pre-treatment but still \>5%; and Hematologic Improvement - hemoglobin increase by \> 1.5g/dl or decreased transfusions by at least 4/8 week period, platelet absolute increase of \>30 X 10\^9/L for those starting at \>20 X 10\^9/L . For those \< 20 X 10\^9 /L at baseline increase by 100%.

  At Completion of Course 3 (Day 63)

Secondary Outcomes (2)

• Correlative Laboratory Studies

  Pre-Study and After 3 Cycles

• Correlation of Cell Alterations With Clinical Response

  Pre-Study and After 3 Cycles

Study Arms (1)

Velcade + Vorinostat

EXPERIMENTAL

This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles.

Drug: bortezomib; Drug: vorinostat

Interventions

bortezomib DRUG

1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle

Also known as: Velcade

Velcade + Vorinostat

vorinostat DRUG

400 mg orally (po) every day on days 1-14 of a 21 day cycle

Also known as: suberoylanilide hydroxamic acid (SAHA)

Velcade + Vorinostat

Eligibility Criteria

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

You may qualify if:

• Disease Specific Criteria: Pathologic Diagnosis must be confirmed by University of Minnesota Hematopathology
• Myelodysplastic Syndrome (MDS): By IPSS Category: INT-2 or High risk, By WHO Classification: RAEB-1 or RAEB-2,By cytogenetics: High Risk Cytogenetic Abnormality Present as defined by the presence Monosomy 7 or complex karyotype. Patients will be eligible after progressing through standard therapy with either Azacitidine or Decitabine. Patients with a history of 5q minus syndrome may be eligible after progressing through treatment with Lenalidomide.
• Acute Myelogenous Leukemia (AML): Histologic subtypes M0,M1,M2,M4,M5,M6,M7 are eligible and must meet one of the three criteria below:
• Refractory Disease/Induction Failure: Failure to achieve initial remission after 2 lines of induction therapy.
• Relapsed Disease
• Newly diagnosed/untreated AML: Patients who are not able to tolerate potentially curative conventional induction chemotherapy due to advanced age, end organ limitations, or performance status limitation will be eligible.
• Additionally, those that refuse conventional induction therapy will be eligible.
• Patients must have relatively stable bone marrow function during the week prior to enrollment on the study. White Blood cells (WBC) may be controlled with hydrea. Rapid WBC doubling not responsive to control with hydrea would indicate unstable bone marrow function. Ideally WBC should be \< 15 X 10\^3 /dl at time of study enrollment.
• Age \>18 years
• Karnofsky performance status \> or = 60%
• Have acceptable organ function as defined within 28 days of enrollment:
• Hematologic: hemoglobin \> 8 g/dL, and platelets \> 20k. (Patients may receive transfusions of either peripheral red blood cells (PRBC) or platelets to achieve these levels)
• Renal: creatinine \< or = 2.0 mg/dL or creatinine clearance \> or = 40 ml/min
• Hepatic: ALT, AST \< or = 2.5 x upper limit of normal and total bilirubin \< or = 1.5 X ULN
• Cardiac: left ventricular ejection fraction \> 40% (testing required for all patients. For those with prior cardiac history (defined as prior stent or bypass surgery) a stress test within 1 month prior to proceeding with the study will be required. A cardiology consult will be required for those with prior documented cardiac disease or those with any significant EKG/ECHO abnormalities found on screening tests.

You may not qualify if:

• Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test within 72 hours prior to study drug administration to rule out pregnancy.
• Grade 2 or greater peripheral neuropathy within 14 days before enrollment
• Active central nervous system (CNS) disease. Patients with any clinical symptoms of active CNS disease must have LP with negative cytology.
• WBC and Peripheral Blast count uncontrolled with hydroxyurea
• Evidence of QT prolongation with QTc interval greater than 0.5 seconds. QTc calculation from the EKG machine will be used for this assessment.
• Clinical evidence of heart failure or history of uncontrolled hypertension. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patients with untreated positive blood cultures or progressive infections as assessed by radiographic studies
• Patients with prior use of other histone deacetylase inhibitors (excluding valproic acid for seizures with a 30 day wash-out period)
• Known hypersensitivity to Velcade, boron or any of the other agents used in this study
• Patients with a history of deep vein thrombosis/pulmonary embolism (DVT/PE) that has not been adequately treated with systemic anticoagulation or that has been recently diagnosed (within the last 2 months).
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Active HIV or viral hepatitis infection
• Other active and potentially life threatening malignancies excluding localized basal cell or squamous cell skin cancers, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Merck Sharp & Dohme LLC: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Congenital Abnormalities

Interventions

Bortezomib; Vorinostat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Erica Warlick, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

ewarlick@umn.edu

612-625-5467

Study Officials

• Erica Warlick, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2009
• First Posted: January 8, 2009
• Study Start: January 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: December 28, 2017
• Results First Posted: February 25, 2013

Record last verified: 2017-12

Locations

US (1)