PAD. ICORG 05-01, V11

NCT00814541 | Completed Phase 2

• 4 other identifiers: 05-01 ICORGICORG-05-012005-000395-41EU-20893
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 9

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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Response rate (complete and partial response)

  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 Outcomes (3)

• Progression-free survival

  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.

• Overall survival

  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.

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

  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.

Study Arms (3)

1

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone

2

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone

3

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone

Interventions

Bortezomib DRUG

1; 2; 3

Doxorubicin DRUG

1; 2; 3

Dexamethasone DRUG

1; 2; 3

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cancer Trials Ireland: lead

Study Sites (9)

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

Dublin, 24, Ireland

Location

Mater Misericordiae University Hospital

Dublin, 7, Ireland

Location

St. James's Hospital

Dublin, 8, Ireland

Location

University College Hospital

Galway, Ireland

Location

Mid-Western Cancer Centre at Mid-Western Regional Hospital

Limerick, 0009, Ireland

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Saint Bartholomew's Hospital

London, England, EC1A 7BE, United Kingdom

Location

University College Hospital

London, England, NW1 2BU, United Kingdom

Location

Belfast City Hospital Trust Incorporating Belvoir Park Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Doxorubicin; Dexamethasone

Condition Hierarchy (Ancestors)

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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Curly Morris

  Belfast City Hospital Trust Incorporating Belvoir Park Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2008
• First Posted: December 25, 2008
• Study Start: December 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2012
• Last Updated: December 31, 2014

Record last verified: 2014-01

Locations

GB (4); IE (5)