Bortezomib for Low or Intermediate-1 Myelodysplastic Syndrome (MDS) With p65 Activation

NCT01891968 | Completed Phase 2 Results

• 2 other identifiers: 2012-0562NCI-2013-01730
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if bortezomib can help to control MDS. The safety of this drug will also be studied. Bortezomib is designed to block a protein that causes cells to grow. This may cause cancer cells to die.

Conditions

Leukemia

Keywords

Leukemia; Myelodysplastic syndrome; MDS; Low or intermediate-1; Bortezomib; Velcade; LDP-341; MLN341; PS-341

Outcome Measures

Primary Outcomes (1)

• Overall Response (OR)

  Primary outcome is overall response (OR) including hematologic improvement defined by International Working Group (IWG), complete remission, partial remission and marrow complete remission.

  8 weeks

Study Arms (1)

Bortezomib

EXPERIMENTAL

Bortezomib administered via subcutaneous route at a dose of 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21 day cycle. A course of treatment will be 21 days.

Drug: Bortezomib

Interventions

Bortezomib DRUG

1.3 mg/m2 subcutaneously on days 1, 4, 8 and 11 of a 21 day cycle.

Also known as: Velcade, LDP-341, MLN341, PS-341

Bortezomib

Eligibility Criteria

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

You may qualify if:

• Voluntary signed informed consent before performance of any study-related procedure not part of normal medical care, indicating that that the patient is aware of the investigational nature of the study in keeping with the policies of MD Anderson Cancer Center (MDACC) and with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Presence of phosphorylated p65 NF-kB component in at least 5% of bone marrow cells
• Age \>/= 18 years of age at time of signing consent
• Confirmed MDS by bone marrow biopsy according to World Health Organization (WHO) or French-American-British (FAB) criteria.
• Classification by the International Prognostic Score System (IPSS) as low or intermediate-1 risk MDS according to cytogenetics, blood cytopenias and % bone marrow blasts within 28 days of the first dose of treatment in this study.
• Patients must have received at least one prior therapy for MDS. Patients could have received transplant for MDS
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.
• Adequate liver function: Total bilirubin \</= 1.5 × the upper limit of normal (ULN), unless presence of Gilbert's Syndrome. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \</= 2.5 × ULN or \</= 5.0 ULN if hepatic involvement is present as determined by the investigator
• Adequate renal function: Serum creatinine \</= 2 mg/dL or a calculated creatinine clearance of \>/= 50 mL/min (using the Cockcroft and Gault method).
• Male patients, even if surgically sterilized (ie, status postvasectomy), who agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study treatment, or agree to completely abstain from heterosexual intercourse.
• Female patients who are postmenopausal for at least 1 year before the Screening visit, or are surgically sterile, or if they are of childbearing potential, must have a negative pregnancy test within 72 hours of treatment start date and agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Significant medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol, or to complete the study.
• Any severe concurrent disease or condition (including active, uncontrolled systemic infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia) that, in the judgment of the Investigator, would make the patient inappropriate for study participation.
• Pregnant or lactating females.
• Patient has \>/= Grade 2 peripheral neuropathy
• Patient had 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 must be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron, or mannitol
• Current diagnosis of another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Treatment with other investigational agents, chemotherapy, or immunotherapy within 14 days of the start of this trial and throughout the duration of this trial.
• Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Guillermo Garcia-Manero, MD
• Organization: The University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-745-3428

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 28, 2013
• First Posted: July 3, 2013
• Study Start: August 7, 2013
• Primary Completion: January 18, 2017
• Study Completion: January 18, 2017
• Last Updated: April 23, 2018
• Results First Posted: April 23, 2018

Record last verified: 2018-03

Locations

US (1)