PAD. ICORG 05-01, V11

NCT ID: NCT00814541

Last Updated: 2014-12-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2012-12-31

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

refractory multiple myeloma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

2

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

3

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Interventions

Bortezomib

Intervention Type: DRUG

Doxorubicin

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients aged at least 18 years with MM requiring therapy for relapsed or refractory disease.

2. Previous VAD or VAD-like therapy (maximum 6 courses standard VAD). Subgroup allocation is shown in 4.1

3. Measurable serum and/or urine paraprotein, or serum free light chain

4. Performance Status (PS) 0-3 (ECOG - see Appendix B)

5. Serum bilirubin values <1.5 times the upper limit of normal

6. Serum ALT/AST values <2.5 times the upper limit of normal

7. Able to give informed consent

Exclusion Criteria

1. 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

2. Men with partners of child bearing potential unwilling to use a medically acceptable form of contraception

3. Patients with non-secretory MM and no measurable elevation of serum free light chain

4. Performance status 4 (ECOG)

5. Patient has a platelet count <75 x 10^9/L within 14 days before enrolment

6. Patient has an absolute neutrophil count <1.0 x 10^9/L within 14 days before enrolment

7. Patient has a serum creatinine > 400 micromol/l at the time of enrolment

8. 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

9. Cardiac ejection fraction <40% by echocardiography or MUGA scan

10. Known HIV seropositivity (obligatory testing is not necessary)

11. Known Hepatitis B or C (obligatory testing is not necessary)

12. Patients who have received more than one autologous transplant

13. 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

14. Previous Bortezomib therapy

15. Patients who have a medical or psychiatric condition which, in the opinion of the investigator, contraindicates the patient's participation in this study

16. 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

17. Plasma exchange within 21 days of enrolment

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

Sponsors

Cancer Trials Ireland

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Curly Morris

Role: PRINCIPAL_INVESTIGATOR

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Locations

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

Dublin, , Ireland

Mater Misericordiae University Hospital

Dublin, , Ireland

St. James's Hospital

Dublin, , Ireland

University College Hospital

Galway, , Ireland

Mid-Western Cancer Centre at Mid-Western Regional Hospital

Limerick, , Ireland

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Saint Bartholomew's Hospital

London, England, United Kingdom

University College Hospital

London, England, United Kingdom

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, United Kingdom

Countries

Ireland; United Kingdom

Other Identifiers

ICORG-05-01

Identifier Type: -

Identifier Source: secondary_id

2005-000395-41

Identifier Type: -

Identifier Source: secondary_id

EU-20893

Identifier Type: -

Identifier Source: secondary_id

05-01 ICORG

Identifier Type: -

Identifier Source: org_study_id

NCT00567138

Identifier Type: -

Identifier Source: nct_alias