Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma
This phase II trial investigates whether patients greater than or equal to 65 years of age diagnosed with myeloma or another plasma cell malignancy will have better outcomes with transplant followed by maintenance therapy, as primarily measured by progression-free survival, versus non-transplant approaches.
Isolated Plasmacytoma of Bone
Light Chain Deposition Disease
Primary Systemic Amyloidosis
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Procedure: autologous stem cell transplant
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Single Autologous Transplant Followed by Consolidation and Maintenance for Participants ≥ 65 Years of Age Diagnosed With Multiple Myeloma or a Related Plasma Cell Malignancy|
- PFS [ Time Frame: From the start of DPACE for all participants who have had at least one day of protocol treatment, assessed up to 4 years ] [ Designated as safety issue: No ]Estimated with the method of Kaplan-Meier and modeled as functions of clinicopathological factors with Cox regression.
- Severe complications (ICU admission, death), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]Frequencies of toxicities will be tabulated on all participants who have completed at least one day of induction therapy. Toxicities will be compared descriptively to historical controls.
- Percentage of participants able to complete full course of therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Complete response (CR) rate using the International Myeloma Working group uniform response criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Summarized with binomial proportions.
- Event free survival [ Time Frame: Time from initial study enrollment to progression/relapse of disease or death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]Estimated with the method of Kaplan-Meier and modeled as functions of clinicopathological factors with Cox regression.
- Overall survival [ Time Frame: Time from initial study enrollment to death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: autologous stem cell transplant
Induction : DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.
After collection, participants will receive dexamethasone x 4 days every 14 days.
Transplant: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.
Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.
Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide)
Maintenance: Year 1 - VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.
Other Names:Drug: cisplatin
Other Names:Drug: doxorubicin
Other Names:Drug: cyclophosphamide
Given IV or PO
Other Names:Drug: etoposide
Other Names:Drug: bortezomib
Other Names:Drug: thalidomide
Other Names:Drug: melphalan
Other Names:Procedure: autologous stem cell transplant
I. To evaluate the progression-free survival (PFS) from the start of dexamethasone, cisplatin, Adriamycin (doxorubicin),Cytoxan (cyclophosphamide), etoposide (DPACE) for all participants who have had at least one day of protocol treatment.
II. To evaluate how well such therapy is tolerated in patients mainly over the age of 65 years by assessing severe complications (intensive care unit [ICU] admission, death) and the percentage of participants able to complete the full course of therapy.
I. To evaluate Quality-Of-Life post-transplant using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30 and QLC-MY20.
INDUCTION THERAPY: Patients receive dexamethasone orally (PO) on days 1-4 and 8-11, cisplatin intravenously (IV) continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV, and etoposide IV on days 1-4. Patients then receive pegfilgrastim subcutaneously (SQ) on days 6 and 13 and undergo collection of stem cells when white blood cell (WBC) and cluster of differentiation (CD)34 counts are within program range. Following stem cell collection, patients may receive interim dexamethasone PO on days 1-4, every 14 days at the discretion of the treating physician.
TRANSPLANT: Beginning between 4 weeks to 6 months after the first day of induction therapy, patients receive as transplant conditioning regimen dexamethasone PO on days -4 to -1 and days +2 through +5, bortezomib IV bolus on days -4, -1, 2, and 5, thalidomide PO on days -4 to 5, and melphalan IV on days -4 and -1. Patients undergo autologous peripheral blood stem cell transplant (PBSCT) on day 0. Between transplant and consolidation therapy, patients receive dexamethasone PO on days 1-4 every 21 days and thalidomide PO daily.
CONSOLIDATION THERAPY: If administered, post-transplant consolidation may begin 4-6 weeks after transplant but should occur no more than 4 months later. Most patients will not receive consolidation. Those that do will receive dexamethasone PO on days 1-4 and 8-11, thalidomide PO on days 1-11, bortezomib IV on days 1, 4, 8, and 11, cisplatin IV continuously, doxorubicin hydrochloride IV continuously, cyclophosphamide IV continuously, and etoposide IV continuously on days 1-4.
MAINTENANCE THERAPY YEAR 1: Beginning 6 weeks-6 months after consolidation therapy or 4 weeks to 6 months after transplant if consolidation is skipped, patients receive bortezomib IV bolus on days 1, 4, 15, and 18, thalidomide PO QD on days 1-28, and dexamethasone PO on days 1-4 and 15-18. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY YEAR 2: Patients receive bortezomib IV on days 1, 4, 15, and 18, cyclophosphamide PO or IV on days 1 and 15, and dexamethasone PO QD on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at least once annually at the study center, but serum for MM marker results will be sent to the study site for close monitoring of PFS .
Please refer to this study by its ClinicalTrials.gov identifier: NCT01849783
|United States, Iowa|
|University of Iowa Hospitals and Clinics||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Guido J. Tricot 319-356-3425 email@example.com|
|Principal Investigator: Guido J. Tricot|
|Principal Investigator:||Guido Tricot||University of Iowa|