Effect of AT7519M Alone and AT7519M Plus Bortezomib in Patients With Previously Treated Multiple Myeloma

NCT ID: NCT01183949

Last Updated: 2024-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-03-31

Brief Summary

The purpose of this study is to determine whether AT7519M alone or AT7519M plus bortezomib are effective treatments in patients with previously treated multiple myeloma.

Detailed Description

The clinical study AT7519M/0004 is an open-label multicenter study to investigate the efficacy of AT7519M alone and AT7519M in combination with bortezomib in patients with previously treated multiple myeloma (MM).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Patients will be enrolled into 3 groups which will run sequentially. Groups A and B will receive AT7519M only, whereas Group C will receive AT7519M in combination with Bortezomib.

Group Type: EXPERIMENTAL

AT7519M

Intervention Type: DRUG

Part A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities.

Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy.

Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose.

Bortezomib

Intervention Type: DRUG

Part C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design. The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2.

Interventions

AT7519M

Part A: Nine patients will receive AT7519M as an intravenous infusion on days 1, 4, 8 and 11 of a three week cycle. The starting dose of AT7519M will be 21mg/m^2/dose and will be increased to 27mg/m^2/dose during subsequent cycles in the absence of AT7519M-related toxicities.

Part B: Amendment clarified there will be no further exploration of AT7519M as a monotherapy.

Part C: Amendment modified dose escalation to a conventional 3 + 3 design with a maximum total of 14 patients will be treated at the maximum tolerated dose.

Intervention Type: DRUG

Bortezomib

Part C will treat between 3-26 patients with a combination of bortezomib and AT7519M in a dose escalation design. The starting doses for the dose escalation are bortezomib 1 mg/m2 and AT7519M 14 mg/m2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ability to understand the risks of the study and provide signed informed consent
• Age 18 years or older
• Relapsed and or Refractory MM
• Disease progression following at least two systemic treatments for MM
• Patient must be refractory to the last bortezomib
• ECOG performance status 0, 1 or 2

Exclusion Criteria

• Pregnant or lactating females. Patients of childbearing potential must use appropriate birth control throughout the study
• Inadequate liver function
• Renal impairment
• Neutrophil count <1.0 x 10^9 /litre in the absence of growth factors
• Platelet count <50 x 10^9 /litre in patients in whom <50% of bone marrow nucleated cells are plasma cells and <30 x 10^9 /litre in patients in whom ≥50 % of bone marrow nucleated cells are plasma cells
• Hemoglobin <8g/dl in the absence of transfusion
• Treated corrected calcium >ULN
• Serum creatine phosphokinase >ULN
• All previous cytotoxic therapies for MM must have been completed at least four weeks prior to treatment with AT7519M (two weeks for all non-cytotoxic therapy)
• Patients may be receiving concomitant therapy with biphosphonates and low dose corticosteroids. Bisphosphonates doses should be stable for at least 30 days prior to study drug administration. Corticosteroids doses should be stable for at least 7 days prior to study treatment
• Prior peripheral stem cell transplant within 12 weeks
• Evidence of mucosal or internal bleeding and/or platelet transfusion refractory (unable to maintain a platelet count >50 x 10^9 /litre)
• Ongoing infection requiring treatment
• Previous radiotherapy within 2 weeks of the start of the study
• Having previously received treatment with a cyclin-dependent kinase or GSK3beta inhibitor
• Incomplete recovery from previous radiotherapy other than residual cutaneous effects or stable < Grade 2 gastrointestinal toxicity
• Prior radiotherapy to the head and neck region for head and neck tumors
• Previous malignancy, except for non-melanomatous skin carcinomas, in situ carcinomas or malignancies with low risk of recurrence.
• Any severe or uncontrolled systemic conditions (e.g. systemic infection) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
• Incomplete recovery from surgery other than stable < Grade 2 toxicity
• Peripheral neuropathy > Grade 2
• Abnormal left ventricular ejection fraction (< lower limit of normal for the institution for a patient of that age) on echocardiogram
• History of an ischemic cardiac event, including myocardial infarction within 3 months of study entry
• Congestive cardiac failure of ≥ grade 3 severity according to NYHA functional classification
• Unstable cardiac disease
• History or presence of bradycardia (≤60bpm), left bundle branch block, heart block, cardiac pacemaker or significant atrial tachyarrhythmias
• If the patient will receive bortezomib (Velcade) during part C of the study, concurrent treatment with any medication known strongly to inhibit or induce CYP3A4, CYP1A2 and CYP2C19 which cannot be discontinued at least two week prior to treatment with AT7519M (other than corticosteroids)
• Concurrent treatment with any medication that prolongs QT interval and may induce Torsades de Pointes and which cannot be discontinued at least two weeks prior to treatment with AT7519M
• Family or personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy
• Previous history of drug-induced QTc prolongation
• Screening 12-lead ECG with measurable QTc interval according to Fridericia's Correction of >450 msecs
• Screening 12-lead ECG with ST depression >1 mm in 2 or more leads or T wave inversion in 2 or more contiguous leads
• Prior history of infection with human immunodeficiency virus (HIV), known active hepatitis B or C viruses
• Diffuse infiltrative pulmonary or pericardial disease
• Known hypersensitivity to bortezomib, boron or any of the excipients of VelcadeTM
• Epilepsy or other convulsive disorder requiring active management
• Serious psychiatric illness, active alcoholism or drug addiction that may hinder or confuse follow up evaluation

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Multiple Myeloma Research Consortium

NETWORK

Sponsor Role: collaborator

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Faber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Centre

New York, New York, United States

MCW and Froedtert Clinical Cancer Center, Division of Neoplastic Diseases & Related Disorders

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

AT7519M/0004

Identifier Type: -

Identifier Source: org_study_id