Relapse Myeloma; Cyclofosfamide; Bortezomib; Maintenance

Multiple Myeloma Clinical Trial

— REMM  

Official title:

Bortezomib in Combination With Continuous Low-dose Oral Cyclophosphamide and Dexamethason Followed by Maintenance in Primary Refractory or Relapsed Bortezomib naïve Multiple Myeloma Patients. A Prospective Phase II Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02467010
• Other study ID #: UMCG REMM
• Secondary ID: 2008-004822-17
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2014
• Last updated: June 8, 2015
• Start date: September 2008
• Est. completion date: July 2013

Study information

• Verified date: June 2015
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib
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.
• Cyclophosphamide
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.
• Dexamethasone
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.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity of induction chemotherapy according to CTCAE version 3.0		5 years	No
Secondary	Progression Free Survival		5 years	No
Secondary	Overall Survival		5 years	No