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

NCT01183949 | Completed Phase 1

• 1 other identifier: AT7519M/0004
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

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.

Conditions

Multiple Myeloma

Keywords

Neoplasms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bortezomib; Antineoplastic Agents

Outcome Measures

Primary Outcomes (1)

• To evaluate the clinical efficacy of AT7519M alone or in combination with bortezomib

  Efficacy will be assessed using the International Multiple Myeloma Working Group (IMWG) Response Criteria

  Subjects with be followed until disease progression (an average of 4 cycles per subject. i.e an average of 84 days)

Secondary Outcomes (3)

• Assess the type, incidence and severity of clinically significant treatment emergent adverse events as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V 4.03

  Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)

• To define the pharmacokinetic profile of AT7519M and bortezomib when administered alone or in combination with bortezomib

  2 cycles (i.e an average of 42 days)

• To identify the maximum tolerated dose (MTD) of AT7519M in combination with bortezomib

  Subjects with be followed until disease progression (an average of 4 cycles per subject, i.e an average of approximately 84 days)

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: AT7519M; Drug: Bortezomib

Interventions

AT7519M 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.

Treatment

Bortezomib 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.

Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead
• Multiple Myeloma Research Consortium: collaborator

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, MA02115, United States

Location

Dana Faber Cancer Institute

Boston, Massachusetts, United States

Location

Memorial Sloan-Kettering Cancer Centre

New York, New York, 10065, United States

Location

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

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemic and Lymphatic Diseases; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 18, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: March 1, 2015
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

US (5)