A Study of Efficacy of Treatment With Bortezomib (in Combination With Doxorubicin and Dexamethasone) in Previously Untreated Patients With Multiple Myeloma

NCT ID: NCT00872521

Last Updated: 2014-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2011-11-30

Brief Summary

The purpose of this study is to determine efficacy of treatment with bortezomib (in combination with doxorubicin and dexamethasone) in previously untreated patients with Multiple Myeloma.

Detailed Description

This is an open-label, single-arm, multicentre study which will enroll approximately 105 patients. Open-label means all people involved in the study know the identity of the intervention. Single-arm means there is one group of patients, all receiving the same treatment. Four 21-day cycles of a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12) (PAD) will be given. Patients will be discontinued if disease progresses, or unacceptable treatment-related toxicity occurs. Following PAD treatment, patients will have peripheral blood stem cells (PBSC) collected, and an autologous stem cell transplant (ASCT) will be performed. Patients will then make monthly visits to the Study Doctor until 1 year after start of treatment, and attend a final follow-up visit at 2 years. Efficacy assessment of response to PAD will be made using the International Myeloma Working Group (IMWG) criteria. The primary outcome is to compare the overall response rate following 4 cycles of PAD induction therapy between patients with and without extra copies of the long arm of the first chromosome (1q21) measured by fluorescent in situ hybridisation (FISH) in their marrow at baseline. Patient reported outcomes will be assessed using the AQoL (Assessment of Quality of Life). Safety will be evaluated throughout the study by assessment of adverse events including changes in physical examination, concomitant medication, ECOG (Eastern Cooperative Oncology Group) scores, vital signs and clinical laboratory findings. A sample size of 105 provides 80% power (a=0.05) to detect a difference in overall response rate of 28% at the end of 4 cycles of PAD. This is based on the assumptions that 44% of patients have amplification of 1q21 1, 2, the overall response rate with PAD combination therapy is 80%; the overall response rate with PAD if PAD therapy does not overcome 1q21 amplification is assumed to be 64%, while without 1q21 amplification it is assumed to be 92%. That is: Overall Response Rate (ORR) = P1q21 amplified x ORRamplified + P1q21 not amplified x ORRnot amplified i.e. 80% = 44% x 64% + 56% x 92%. The sample size of 105 allows for a 20% drop-out rate. Four 21-day cycles of PAD: a combination of bortezomib i.v. (intravenous) 1.3 mg/m2 (Days 1, 4, 8 and 11), doxorubicin i.v. 20 mg/m2 (days 1 and 4) and dexamethasone p.o. (by mouth) (days 1, 2, 4, 5, 8, 9, 11 and 12).

Conditions

Multiple Myeloma

Study Design

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

Study Groups

bortezomib; doxorubicin; dexamethasone

PAD induction Open Label Treatment: Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1 4 8 \& 11) Doxorubicin 20 mg/m2 i.v. (D1 \& 4) Dexamethasone 20 mg p.o. (D1 2 4 5 8 9 11 \& 12)

Group Type: EXPERIMENTAL

PAD induction

Intervention Type: DRUG

Open Label Treatment:

Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1, 4, 8 & 11), Doxorubicin 20 mg/m2 i.v. (D1 & 4), Dexamethasone 20 mg p.o. (D1, 2, 4, 5, 8 , 9, 11 & 12)

Interventions

PAD induction

Open Label Treatment:

Four 21-day Treatment Cycles Bortezomib 1.3 mg/m2 i.v. (D1, 4, 8 & 11), Doxorubicin 20 mg/m2 i.v. (D1 & 4), Dexamethasone 20 mg p.o. (D1, 2, 4, 5, 8 , 9, 11 & 12)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Previously diagnosed with multiple myeloma
• eligible for autologous stem cell transplantation
• meets pre-treatment lab criteria (as defined within protocol).

Exclusion Criteria

• Previously received treatment for multiple myeloma (including prior therapy with radiation or pulsed dexamethasone), except localised radiation to a solitary lesion or plasmacytomas or 4 days of corticosteroid therapy
• have a current diagnosis of smoldering multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or Waldenström Macroglobulinemia
• have a history of any other malignancy within 5 years before enrolment
• have other significant comorbidities.

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

Sponsors

Janssen-Cilag Pty Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag Pty Ltd Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag Pty Ltd

Locations

Adelaide, , Australia

Box Hill, , Australia

Brisbane, , Australia

Camperdown, , Australia

Geelong, , Australia

Gosford, , Australia

Greenslopes, , Australia

Malvern, , Australia

Melbourne, , Australia

Parkville, , Australia

Perth, , Australia

Sydney, , Australia

Westmead, , Australia

Woden, , Australia

Wollongong, , Australia

Woolloongabba, , Australia

Countries

Australia

Other Identifiers

26866138MMY2059

Identifier Type: OTHER

Identifier Source: secondary_id

PIMMS Trial

Identifier Type: OTHER

Identifier Source: secondary_id

CR015640

Identifier Type: -

Identifier Source: org_study_id