Bortezomib and Doxil for the Treatment of Patients With Acute Myelogenous Leukemia

NCT01736943 | Completed Phase 2 Results DMC

• 3 other identifiers: 322070UCDCC#230X05385
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether bortezomib in combination with doxil/lipodox is effective in the treatment of Acute Myeloid Leukemia.

Conditions

Acute Myelogenous Leukemia

Keywords

Bortezomib; Doxil

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up.

  Up to 2 years

Secondary Outcomes (2)

• Overall Survival

  Up to two years

• Toxicity Information Recorded Will Include the Type, Severity, Time of Onset, Time of Resolution, and the Probable Association With the Study Regimen.

  Up to two years

Study Arms (1)

Bortezomib + Doxil

EXPERIMENTAL

Bortezomib will be given subcutaneously at 1.5mg/m2 on days 1, 4, 8 and 11 of a 3 week cycle. Doxil will be administered once every three weeks as a single intravenous infusion at a dose of 40 mg/m2 (day 4 of each cycle).

Drug: Bortezomib; Drug: Doxil

Interventions

Bortezomib DRUG

Bortezomib will be given twice a week subcutaneously (under the skin) for two weeks in every 3 week cycle.

Also known as: Velcade

Bortezomib + Doxil

Doxil DRUG

Doxil or LipoDox will also be given through a venous catheter (inside your vein). Doxil or LipoDox will be given over 60 to 90 minutes on Day 4 of every 21-day cycle.

Also known as: LipoDox; pegylated liposomal doxorubicin

Bortezomib + Doxil

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Female subjects must be either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of SQ VELCADE, or agree to completely abstain from heterosexual intercourse.
• Male subjects, even if surgically sterilized must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
• Adults (age 18 to 80) with AML, excluding the M3 subtype, that are not likely to respond to conventional therapy
• Bone marrow and peripheral blood studies must be available for confirmation of diagnosis.
• Performance status of 60% or greater by the Karnofsky scale
• A minimum of 4 weeks must have elapsed since the completion of prior chemotherapy.
• Patients may have had autologous transplant.
• There are no minimum hematological parameter requirements prior to the first two cycles, as patients with AML and myelodysplastic syndrome (MDS) are understood to have low absolute neutrophil count (ANC) and platelet counts when the disease is active. However, patients with white blood cell count (WBC) greater than 30,000 will receive hydroxyurea to reduce the WBC count to below 30,000 at which point they may begin treatment.
• A pretreatment calculated creatinine clearance (absolute value) of ≥ 40 ml/minute or serum creatinine of \< 1.5 x upper limit of normal is required.
• Patients must have a serum bilirubin ≤1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤2.5 times the institutional upper limits of normal.

You may not qualify if:

• There is no specific platelet and absolute neutrophil count that will exclude patients from this study given the natural history of AML.
• Patient has greater than or equal to Grade 2 peripheral neuropathy
• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association 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. An left ventricular ejection fraction (LVEF) must be \> 50
• Patient has hypersensitivity to VELCADE, boron, or mannitol.
• Female subject is pregnant or lactating.
• Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 3 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.
• Participation in clinical trials with other investigational agents not included in this trial, 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.
• Patients with active/uncontrolled central nervous system (CNS) leukemia
• Patients eligible, at the time of starting treatment, for curative therapeutic approaches (such as allogeneic transplant) are not eligible for the trial.
• Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study other than hydroxyurea for control of counts.
• Human Immunodeficiency Virus (HIV)-positive.

Sponsors & Collaborators

• Joseph Tuscano: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of California Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Bortezomib; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic 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: Analyst
• Organization: University of California, Davis

nlogihara@ucdavis.edu

916-734-8053

Study Officials

• Joseph Tuscano, MD

  University of California, Davis

  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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 26, 2012
• First Posted: November 29, 2012
• Study Start: December 19, 2012
• Primary Completion: May 20, 2019
• Study Completion: May 20, 2019
• Last Updated: February 24, 2021
• Results First Posted: February 24, 2021

Record last verified: 2021-02

Locations

US (1)