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PAD. ICORG 05-01, V11

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Bortezomib

Doxorubicin

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

Patients aged at least 18 years with MM requiring therapy for relapsed or refractory disease.
Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup allocation is shown in 4.1
Measurable serum and/or urine paraprotein, or serum free light chain
Performance Status (PS) 0-3 (ECOG - see Appendix B)
Serum bilirubin values <1.5 times the upper limit of normal
Serum ALT/AST values <2.5 times the upper limit of normal
Able to give informed consent

Exclusion criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

Females of child-bearing potential without a negative pregnancy test, immediately prior to the start of PAD therapy and/or unwilling to use barrier contraceptive precautions throughout the study or who are pregnant or breast-feeding
Men with partners of child bearing potential unwilling to use a medically acceptable form of contraception
Patients with non-secretory MM and no measurable elevation of serum free light chain
Performance status 4 (ECOG)
Patient has a platelet count <75 x 10^9/L within 14 days before enrolment
Patient has an absolute neutrophil count <1.0 x 10^9/L within 14 days before enrolment
Patient has a serum creatinine > 400 micromol/l at the time of enrolment
Patient has Grade 2 or greater than Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) within 14 days before enrolment
Cardiac ejection fraction <40% by echocardiography or MUGA scan
Known HIV seropositivity (obligatory testing is not necessary)
Known Hepatitis B or C (obligatory testing is not necessary)
Patients who have received more than one autologous transplant
Use of any investigational drug within 4 weeks prior to enrolment or any patients scheduled to receive any investigational drug during the course of the study
Previous Bortezomib therapy
Patients who have a medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient's participation in this study
Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumours may be entered
Plasma exchange within 21 days of enrolment

Sites / Locations

Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital
Mater Misericordiae University Hospital
St. James's Hospital
University College Hospital
Mid-Western Cancer Centre at Mid-Western Regional Hospital
Leeds Cancer Centre at St. James's University Hospital
Saint Bartholomew's Hospital
University College Hospital
Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm Description

Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously.Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD.

Relapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD.

Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR.

Outcomes

Primary Outcome Measures

Response rate (complete and partial response)

Secondary Outcome Measures

Progression-free survival

Overall survival

Compare original response to vincristine, doxorubicin, and dexamethasone with response to bortezomib, doxorubicin hydrochloride, and dexamethasone

Full Information

NCT ID

NCT00814541

First Posted

December 24, 2008

Last Updated

December 30, 2014

Sponsor

Cancer Trials Ireland

1. Study Identification

Unique Protocol Identification Number

NCT00814541

Brief Title

PAD. ICORG 05-01, V11

Official Title

Phase II Study to Assess the Safety, Efficacy, and Tolerability of Combination Therapy With Velcade (Bortezomib), Doxorubicin, and Dexamethasone (PAD) as Therapy for Patients With Relapsed or Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2014

Overall Recruitment Status

Completed

Study Start Date

December 2005 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cancer Trials Ireland

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with bortezomib may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin and dexamethasone works in treating patients with multiple myeloma that has relapsed or not responded to treatment. PATIENT POPULATION: Patients with relapsed or refractory multiple myeloma requiring therapy will be invited to participate in this study. Eligible patients will be >18 years old and able to give fully informed consent. Patients must have a Performance Score (PS) of 0-3 (ECOG), measurable serum and/or urine paraprotein, or serum free light chain, bilirubin value of less than one and a half times the upper limit of normal with ALT/AST values less than two and a half times the upper limit of normal. Patients with non-secretory multiple myeloma are excluded from this study.

Detailed Description

OBJECTIVES: Primary To assess the response (partial and complete response) in patients with relapsed or refractory multiple myeloma receiving bortezomib, doxorubicin hydrochloride, and dexamethasone (PAD) after prior treatment with a maximum of 6 courses of vincristine, doxorubicin, and dexamethasone (VAD) or VAD-like regimen. Secondary To assess the safety and toxicity of PAD therapy in these patients. To determine the progression-free survival and overall survival of these patients. To compare the original response to VAD with the response obtained with PAD as assessed by percent fall in paraprotein or Bence Jones Protein, lowest level of abnormal protein achieved, and duration of response in these patients. OUTLINE: This is a multicenter study. STUDY DESIGN & METHODOLOGY: This is a non-randomised, open labelled phase II trial in patients with relapsed or refractory multiple myeloma. Patients will be treated with: Bortezomib 1.3mg/m^2 bolus IV injection days 1, 4, 8 & 11 + Dexamethasone 40mg po on days 1, 2, 3, 4 + Doxorubicin 9mg/m^2/day IV continuous infusion over days 1 - 4. In addition, for the first cycle only, Dexamethasone will also be given at 40mg po on days 8 - 11 and 15 - 18. Each treatment regimen will continue for a minimum of four - and up to six - cycles of 21 days (maximum response and 1 cycle). This study planned to recruit a total of 69 patients in up to 8 centres in Ireland and the UK. Patients will be enrolled in three groups of 23 patients: Relapsed patients, previously treated with VAD or VAD like regimen (VAMP, C-VAMP and Z-Dex are examples of VAD like therapy) and who have had autologous transplants at least 1 year previously. Patients may proceed directly to PAD therapy or have had a maximum of one other line of therapy before PAD. Relapsed patients, previously treated with VAD or VAD-like regimen who have not had autologous transplantation and achieved at least PR (Appendix A). Patients may proceed directly to PAD therapy or have had a maximum of two other lines of therapy before PAD. Patients refractory (MR, NC or PD) to VAD or VAD-like therapy. Patients should proceed directly to PAD therapy. Patients with NC or PD may proceed to PAD after a minimum of two cycles of VAD or VAD-like therapy or a minimum of 4 cycles, if MR. After completion of study treatment, patients are followed every 2 months for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Primary Outcome Measure Information:

Title

Response rate (complete and partial response)

Time Frame

Patients will be followed in this study for approximately 16 months after recruitment to cover the period of PAD therapy plus one year follow up. The minimum frequency of reviews will be every two months.

Secondary Outcome Measure Information:

Title

Progression-free survival

Time Frame

Title

Overall survival

Time Frame

Title

Compare original response to vincristine, doxorubicin, and dexamethasone with response to bortezomib, doxorubicin hydrochloride, and dexamethasone

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study: Patients aged at least 18 years with MM requiring therapy for relapsed or refractory disease. Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup allocation is shown in 4.1 Measurable serum and/or urine paraprotein, or serum free light chain Performance Status (PS) 0-3 (ECOG - see Appendix B) Serum bilirubin values <1.5 times the upper limit of normal Serum ALT/AST values <2.5 times the upper limit of normal Able to give informed consent Exclusion criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: Females of child-bearing potential without a negative pregnancy test, immediately prior to the start of PAD therapy and/or unwilling to use barrier contraceptive precautions throughout the study or who are pregnant or breast-feeding Men with partners of child bearing potential unwilling to use a medically acceptable form of contraception Patients with non-secretory MM and no measurable elevation of serum free light chain Performance status 4 (ECOG) Patient has a platelet count <75 x 10^9/L within 14 days before enrolment Patient has an absolute neutrophil count <1.0 x 10^9/L within 14 days before enrolment Patient has a serum creatinine > 400 micromol/l at the time of enrolment Patient has Grade 2 or greater than Grade 2 peripheral neuropathy or neuropathic pain as defined by NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE) within 14 days before enrolment Cardiac ejection fraction <40% by echocardiography or MUGA scan Known HIV seropositivity (obligatory testing is not necessary) Known Hepatitis B or C (obligatory testing is not necessary) Patients who have received more than one autologous transplant Use of any investigational drug within 4 weeks prior to enrolment or any patients scheduled to receive any investigational drug during the course of the study Previous Bortezomib therapy Patients who have a medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient's participation in this study Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumours may be entered Plasma exchange within 21 days of enrolment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Curly Morris

Organizational Affiliation

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Adelaide and Meath Hospital, Dublin Incorporating the National Children's Hospital

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

Mater Misericordiae University Hospital

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

St. James's Hospital

City

Dublin

ZIP/Postal Code

Country

Ireland

Facility Name

University College Hospital

City

Galway

Country

Ireland

Facility Name

Mid-Western Cancer Centre at Mid-Western Regional Hospital

City

Limerick

ZIP/Postal Code

0009

Country

Ireland

Facility Name

Leeds Cancer Centre at St. James's University Hospital

City

Leeds

State/Province

England

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Saint Bartholomew's Hospital

City

London

State/Province

England

ZIP/Postal Code

EC1A 7BE

Country

United Kingdom

Facility Name

University College Hospital

City

London

State/Province

England

ZIP/Postal Code

NW1 2BU

Country

United Kingdom

Facility Name

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

City

Belfast

State/Province

Northern Ireland

ZIP/Postal Code

BT9 7AB

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

PAD. ICORG 05-01, V11

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