Clinical trial NCT01341262: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: autologous stem cell transplantation
thalidomide
induction therapy
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2011-04-25
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Response rate (at least PR, VGPR, nCR and CR) to thal-dex induction
timeFrame: 120 days after the start day of tal-dex induction therapy
measure: duration of response (partial response, PR, very good partial response, VGPR, complete response, CR)
timeFrame: Average time period between the day of first achievement of response and the day of first relapse or progression
measure: time to progression (TTP)
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression
measure: progression free survival (PFS)
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
measure: toxicity of thal-dex (induction and subsequent treatment phases)
timeFrame: Within 30 days after the last dose of study drug
measure: Response rate (at least PR, VGPR, nCR and CR) to first ASCT
timeFrame: 90 days after first ASCT
measure: Response rate (at least PR, VGPR, nCR and CR) to second ASCT
timeFrame: 90 days after second ASCT
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Average time period between the start day of induction therapy and the day of death, due to any cause
measure: OS by cytogenetic abnormalities
timeFrame: Average time period between the start day of induction therapy and the day of death, due to any cause
measure: OS by 18F-FDG PET/CT imaging
timeFrame: Average time period between the start day of induction therapy and the day of death, due to any cause
measure: TTP by cytogenetic abnormalities
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression
measure: PFS by cytogenetic abnormalities
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
measure: TTP by 18F-FDG PET/CT imaging
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression
measure: PFS by 18F-FDG PET/CT imaging
timeFrame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly
Other outcomes:
Locations:
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Michele Cavo, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.