Relapse Myeloma; Cyclofosfamide; Bortezomib; Maintenance

NCT02467010 | Completed Phase 2 DMC

• 2 other identifiers: UMCG REMM2008-004822-17
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

Bortezomib and cyclophosphamide in combination with dexamethasone has already demonstrated high response rates in refractory multiple myeloma. Low dose continuous cyclophosphamide, also called metronomic scheduling, minimize toxic side effects and eliminate the obligatory rest periods. Combining cyclophosphamide with bortezomib might target distinct aspects of a myeloma functionality. The objectives of the present study are whether patients with refractory or relapsed multiple myeloma after reinduction with bortezomib, cyclophosphamide and dexamethasone will benefit from maintenance therapy with bortezomib and cyclophosphamide with acceptable side-effects. Recently two studies have shown with thalidomide that maintenance therapy might improve EFS and one study also the OS.

Conditions

Multiple Myeloma

Keywords

Bortezomib; cyclophosphamide; dexamethason; multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Toxicity of induction chemotherapy according to CTCAE version 3.0

  5 years

Secondary Outcomes (2)

• Progression Free Survival

  5 years

• Overall Survival

  5 years

Study Arms (1)

Bortezomib, cyclophosphamide, dexamethason

EXPERIMENTAL

* To assess the efficacy of bortezomib, cyclophosphamide and dexamethasone during re-induction and in maintenance therapy. * To assess the safety of bortezomib, cyclophosphamide and dexamethasone during re-induction and in maintenance therapy in patients with refractory or relapsed multiple myeloma.

Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Bortezomib DRUG

Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets \> 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.

Also known as: Velcade

Bortezomib, cyclophosphamide, dexamethason

Cyclophosphamide DRUG

Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets \> 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.

Also known as: Endoxan

Bortezomib, cyclophosphamide, dexamethason

Dexamethasone DRUG

Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets \> 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.

Bortezomib, cyclophosphamide, dexamethason

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Stage II-III Multiple Myeloma
• Relapse or primary refractory disease after initial chemotherapy
• WHO performance status 0 - 2
• Life expectancy of at least 6 weeks
• ANC (absolute neutrophil count) ≥ 1.0x109/l(or ≥ 0.5x109/l, if due to bone marrow infiltration by malignancy)
• Platelet count ≥ 75x109/l or ≥ 50x109/l, if due to bone marrow infiltration by malignancy)
• Written informed consent (present in patient's file)
• Patient is able and willing to use adequate contraception during therapy and for at least 1 month after study
• Patient has the ability to understand the requirements of the study

You may not qualify if:

• Previous treatment with bortezomib
• Urine production \< 1.5 l/24h
• Pre-existent polyneuropathy (grade 2 or higher, according to CTCAE 3.0)
• Pregnancy or positive pregnancy tests during study and for 1 month after final dose of thalidomide
• History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin)
• Active uncontrolled infections
• Additional uncontrolled serious medical or psychiatric illness

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Cyclophosphamide; Dexamethasone

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sjoerd Hovenga

  Nij Smellinghe Hospital Drachten

  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: PRINCIPAL INVESTIGATOR
• PI Title: Prof.dr.

Study Record Dates

• First Submitted: February 17, 2014
• First Posted: June 9, 2015
• Study Start: September 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: June 9, 2015

Record last verified: 2015-06

Locations

NL (1)