Back to resultsTHAL-DEX Incorporated Into Double PBSC Autotransplantation for Untreated Multiple Myeloma (MM)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Thalidomide
Dexamethasone
Zoledronic acid
Cyclophosphamide
Melphalan
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring autologous stem cell transplantation, thalidomide, induction therapy
Eligibility Criteria
Inclusion criteria:
- Confirmed diagnosis of symptomatic MM based on standard criteria.
- No prior or current systemic therapy for MM, with exception of steroids.
- At least 18 years and less than 65 years of age.
- Presence of quantifiable M protein in serum or urine.
- Durie & Salmon stage II-III or I with disease progression.
- Adequate organ function (heart, lung).
- No previous deep vein thrombosis and/or recurring thrombophlebitis and/or pulmonary embolisms, confirmed by doppler ultrasound or computed tomography scan.
- Willing and able to comply with the protocol requirements.
Exclusion criteria:
- Diagnosis of smouldering or asymptomatic MM, plasmacell leukemia, solitary plasmocytoma of the bone o extramedullary plasmocytoma.
- Diagnosis of non-secretory MM.
- Prior or current systemic therapy for MM, with exception of steroids.
- More than 65 years of age.
- Female subjects pregnant.
- Non adequate organ function (heart, lung).
- Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
Sites / Locations
Outcomes
Primary Outcome Measures
Response rate (at least PR, VGPR, nCR and CR) to thal-dex induction
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
duration of response (partial response, PR, very good partial response, VGPR, complete response, CR)
Duration of response is calculated from the first achievement of the response (at least PR, at least VGPR, at least CR) to relapse/progression
time to progression (TTP)
TTP is calculated from the start date of induction therapy to the date of relapse/progression
progression free survival (PFS)
PFS is calculated from the start date of induction therapy to the date of relapse/progression or death for any cause, whichever occurs first
toxicity of thal-dex (induction and subsequent treatment phases)
Adverse events are assessed monthly and graded according to the National Cancer Institute Common Toxicity Criteria, version 2. Safety is monitored until 30 days after the last dose of study drug.
Response rate (at least PR, VGPR, nCR and CR) to first ASCT
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
Response rate (at least PR, VGPR, nCR and CR) to second ASCT
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
Secondary Outcome Measures
Overall survival (OS)
OS is measured from the start date of induction therapy until death from any cause
OS by cytogenetic abnormalities
OS is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
OS by 18F-FDG PET/CT imaging
OS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
TTP by cytogenetic abnormalities
TTP is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
PFS by cytogenetic abnormalities
PFS is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
TTP by 18F-FDG PET/CT imaging
TTP is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
PFS by 18F-FDG PET/CT imaging
PFS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
Full Information
NCT ID
NCT01341262
First Posted
March 31, 2011
Last Updated
April 22, 2011
Sponsor
IRCCS Azienda Ospedaliero-Universitaria di Bologna
1. Study Identification
Unique Protocol Identification Number
NCT01341262
Brief Title
THAL-DEX Incorporated Into Double PBSC Autotransplantation for Untreated Multiple Myeloma (MM)
Official Title
Thalidomide-Dexamethasone Incorporated Into Double Autologous Stem-Cell Transplantation for Patients Less Than 65 Years of Age With Newly Diagnosed Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
January 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
IRCCS Azienda Ospedaliero-Universitaria di Bologna
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The marked activity of thalidomide (thal) and dexamethasone (dex) in relapsed and refractory multiple myeloma (MM) provided the basis for this phase 2 clinical study aimed at investigating the efficacy and toxicity of thal-dex incorporated into melphalan-based double autologous stem cell transplantation (ASCT)for patients less than 65 years old with newly diagnosed symptomatic MM. Thal-dex was given as primary induction therapy and was then continued throughout the subsequent treatment phases until the day before the second autotransplantation. Primary study endpoints,as evaluated on an intention to treat basis, are response rates to the different treatment phases (induction, first and second ASCT), best response whenever achieved, duration of response (DOR), time to progression (TTP), progression free survival (PFS)and toxicity profile of thal-dex. Secondary endpoints, as evaluated on an intention to treat basis, are overall survival (OS) and clinical outcomes (DOR, TTP, PFS and OS)according to prognostic factors, including cytogenetic abnormalities and imaging features, as detected by 18F-FDG PET/CT.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
autologous stem cell transplantation, thalidomide, induction therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
378 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Intervention Description
INDUCTION THERAPY: 100 mg/d on days 1-14, 200 mg/d on days 15-120 (in case of delay of HD-CTX , Thalidomide will be continued until the day before Cyclophosphamide as priming therapy for PBSC collection)
AFTER PBSC COLLECTION: 200 mg/d from day after last PBSC collection until the day before first course of MEL-200
AFTER FIRST TRANSPLANTATION: 200 mg/d from recovery of hematopoiesis until the day before the second course of MEL-200
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
INDUCTION THERAPY: 40 mg/d days 1-4, 9-12 and 17-20 (cycles 1 and 3, 30 days each); 40 mg/d days 1-4 (cycles 2 and 4, 30 days each)
AFTER PBSC COLLECTION: 40 mg/d days 1-4 (starting the same day of resumption of Thalidomide)
AFTER FIRST TRANSPLANTATION: 40 mg/d days 1-4 (starting the same day of resumption of Thalidomide) for 3 cycles (30 days each)
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid
Intervention Description
INDUCTION THERAPY: 4 mg i.v. once a cycle for 4 cycles (30 days each)
AFTER PBSC COLLECTION: 4 mg i.v. once (the same day of resumption of Thalidomide)
AFTER FIRST TRANSPLANTATION: 4 mg i.v. once a cycle (starting the same day of resumption of Thalidomide) for 3 cycles (30 days each)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 7 g/sqm + G-CSF 5 mcg/Kg from the day +6 for stem cell mobilisation
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Melphalan 200 mg/sqm on day -1 for first and second ASCT
Primary Outcome Measure Information:
Title
Response rate (at least PR, VGPR, nCR and CR) to thal-dex induction
Description
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
Time Frame
120 days after the start day of tal-dex induction therapy
Title
duration of response (partial response, PR, very good partial response, VGPR, complete response, CR)
Description
Duration of response is calculated from the first achievement of the response (at least PR, at least VGPR, at least CR) to relapse/progression
Time Frame
Average time period between the day of first achievement of response and the day of first relapse or progression
Title
time to progression (TTP)
Description
TTP is calculated from the start date of induction therapy to the date of relapse/progression
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression
Title
progression free survival (PFS)
Description
PFS is calculated from the start date of induction therapy to the date of relapse/progression or death for any cause, whichever occurs first
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
Title
toxicity of thal-dex (induction and subsequent treatment phases)
Description
Adverse events are assessed monthly and graded according to the National Cancer Institute Common Toxicity Criteria, version 2. Safety is monitored until 30 days after the last dose of study drug.
Time Frame
Within 30 days after the last dose of study drug
Title
Response rate (at least PR, VGPR, nCR and CR) to first ASCT
Description
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
Time Frame
90 days after first ASCT
Title
Response rate (at least PR, VGPR, nCR and CR) to second ASCT
Description
Responses are reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive)and VGPR (at least 90% reduction of M component).
Time Frame
90 days after second ASCT
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
OS is measured from the start date of induction therapy until death from any cause
Time Frame
Average time period between the start day of induction therapy and the day of death, due to any cause
Title
OS by cytogenetic abnormalities
Description
OS is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
Time Frame
Average time period between the start day of induction therapy and the day of death, due to any cause
Title
OS by 18F-FDG PET/CT imaging
Description
OS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
Time Frame
Average time period between the start day of induction therapy and the day of death, due to any cause
Title
TTP by cytogenetic abnormalities
Description
TTP is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression
Title
PFS by cytogenetic abnormalities
Description
PFS is calculated as defined above in patients with or without high risk cytogenetic abnormalities (translocation t(4;14), deletion chromosome 17p, deletion chromosome 13q)
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
Title
TTP by 18F-FDG PET/CT imaging
Description
TTP is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression
Title
PFS by 18F-FDG PET/CT imaging
Description
PFS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)
Time Frame
Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Confirmed diagnosis of symptomatic MM based on standard criteria.
No prior or current systemic therapy for MM, with exception of steroids.
At least 18 years and less than 65 years of age.
Presence of quantifiable M protein in serum or urine.
Durie & Salmon stage II-III or I with disease progression.
Adequate organ function (heart, lung).
No previous deep vein thrombosis and/or recurring thrombophlebitis and/or pulmonary embolisms, confirmed by doppler ultrasound or computed tomography scan.
Willing and able to comply with the protocol requirements.
Exclusion criteria:
Diagnosis of smouldering or asymptomatic MM, plasmacell leukemia, solitary plasmocytoma of the bone o extramedullary plasmocytoma.
Diagnosis of non-secretory MM.
Prior or current systemic therapy for MM, with exception of steroids.
More than 65 years of age.
Female subjects pregnant.
Non adequate organ function (heart, lung).
Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Cavo, MD
Organizational Affiliation
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
21900189
Citation
Zamagni E, Patriarca F, Nanni C, Zannetti B, Englaro E, Pezzi A, Tacchetti P, Buttignol S, Perrone G, Brioli A, Pantani L, Terragna C, Carobolante F, Baccarani M, Fanin R, Fanti S, Cavo M. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011 Dec 1;118(23):5989-95. doi: 10.1182/blood-2011-06-361386. Epub 2011 Sep 6. Erratum In: Blood. 2012 Sep 13;120(11):2349.
Results Reference
derived
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THAL-DEX Incorporated Into Double PBSC Autotransplantation for Untreated Multiple Myeloma (MM)
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