Combination Bortezomib-containing Regimens in Newly Diagnosed Patients With t (4; 14) Positive Multiple Myeloma

NCT00570180 | Completed Phase 2 DMC

• 2 other identifiers: 26866138-MMY-2016t4;14 trial PMH
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief Summary

Given the disappointing results with routine ASCT in t(4;14) patients, we propose this open label phase II study of bortezomib along with dexamethasone and pegylated liposomal doxorubicin (Doxil/Caelyx), referred to as the DBd regimen, for 4 cycles, followed by post-induction therapy with cyclophosphamide + bortezomib + prednisone (referred to as the CyBorP regimen) for 8 cycles. Since patients with t(4;14) remain at high risk for relapse, maintenance therapy with dexamethasone weekly will be given until disease progression.

Conditions

Multiple Myeloma

Keywords

newly diagnosed

Outcome Measures

Primary Outcomes (1)

• To determine the time to progression (TTP) with this treatment regimen

  Measured from the date of enrollment to the date of disease progression. Otherwise, censored at the time of last disease assessment. Responses were assessed using the International Myeloma Working Group criteria, involving a modified version of the European Group for Blood and Marrow Transplantation (EBMT) criteria, where the category of stringent complete response (sCR) was included for patients with normalization of the free light chain ratio.10,11 Bone marrow aspirate and biopsy were obtained routinely after induction therapy to confirm CR or sCR. Serum free light chain assay and serum and/or urine electrophoresis were performed monthly; immunofixation was performed when confirmation of very good partial response (VGPR), CR, or sCR was necessary.

  Patients were followed monthly until disease progression and subsequently every six months for up to five years to assess OS.

Secondary Outcomes (4)

• To determine the objective response rate/duration following DBd induction and Cybor P post induction therapy

  Patients were followed monthly until disease progression

• To determine PFS

  5 years

• To determine overall survival

  5 years

• To determine the safety profile of this regimen

  5 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Please see intervention description for Bortezomib (Velcade)

Drug: Bortezomib

Interventions

Bortezomib DRUG

21 day-cycle Induction therapy:bortezomib 1.3 mg/m2 (I.V. Days 1, 4, 8, and 11), then 10-day rest period. DOXIL 30 mg/m2 given after bortezomib (I.V. infusion Day 4 of each cycle). Dexamethasone 40 mg PO on days 1-4,8-11 and 15-18 during the first cycle. Subsequent 3 cycles, dexamethasone 40 mg PO given on days 1-4 and 11-14. Patients who don't progress may undergo elective stem cell mobilization, stem cell collection and cryopreservation. Patients will then receive post-induction therapy 1.5 mg/m2 bortezomib days 1, 8, and 15 I.V. + cyclophosphamide 300 mg/m2 PO weekly + prednisone 100 mg PO on alternate days for 8 monthly 28 day cycles.Maintenance therapy with weekly 40 mg dexamethasone (days 1, 8, 15 and 22) every month until disease progression occurs.

Also known as: Velcade

Single Arm

Eligibility Criteria

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

You may qualify if:

• Patients previously diagnosed with MM based on criteria from the International Myeloma Working Group (IMWG)
• Patients who have 'measurable' disease
• Age 18 years at the time of signing Informed Consent
• A patient may have received up to 4 months of other anti myeloma therapy, as part of the induction therapy, prior enrollment and still be considered eligible to participate in the study, as long as the patient's multiple myeloma has not progressed on the current regimen and the other eligibility criteria are met.
• Patient is t(4;14) positive on screening assay.

You may not qualify if:

• Peripheral neuropathy of Grade 2 or greater.
• Patients with evidence of mucosal or internal bleeding and/or refractoriness to platelet transfusions (i.e., unable to maintain a platelet count 50 x 109 /L).
• Patients with an absolute neutrophil count (ANC) \< 1.0 x 109/L. Treatment to raise the ANC, such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is not allowed within 14 days of study entry.
• Patients with hemoglobin \< 80 g/L despite transfusion.
• Pregnant or lactating women

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Princess Margaret Hospital, Canada: collaborator
• Ortho Biotech, Inc.: collaborator

Study Sites (7)

Cross Cancer Institute 11560 University Ave

Edmonton, Alberta, T6G-1Z2, Canada

Location

CancerCare Manitoba 675 McDermot Ave.

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Queen Elizabeth II Health Sciences Centre.

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

London Regional Cancer Program 790 Commissioners Road East

London, Ontario, N6A 4L6, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Saskatoon Cancer Centre 20 Campus Drive

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Donna E. Reece, MD

  University Health Network, Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

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: December 6, 2007
• First Posted: December 10, 2007
• Study Start: August 25, 2008
• Primary Completion: September 15, 2015
• Study Completion: September 15, 2015
• Last Updated: September 1, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)