THAL-DEX Incorporated Into Double PBSC Autotransplantation for Untreated Multiple Myeloma (MM)

Multiple Myeloma Clinical Trial

Official title:

Thalidomide-Dexamethasone Incorporated Into Double Autologous Stem-Cell Transplantation for Patients Less Than 65 Years of Age With Newly Diagnosed Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01341262
• Other study ID #: MM-BO2002
• Status: Completed
• Phase: Phase 2
• First received: March 31, 2011
• Last updated: April 22, 2011
• Start date: March 2002
• Est. completion date: January 2009

Study information

• Verified date: March 2011
• Source: Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 378
• Est. completion date: January 2009
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, 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:
• Thalidomide
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
• Dexamethasone
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)
• Zoledronic acid
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)
• Cyclophosphamide
Cyclophosphamide 7 g/sqm + G-CSF 5 mcg/Kg from the day +6 for stem cell mobilisation
• Melphalan
Melphalan 200 mg/sqm on day -1 for first and second ASCT

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	120 days after the start day of tal-dex induction therapy	No
Primary	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	Average time period between the day of first achievement of response and the day of first relapse or progression	No
Primary	time to progression (TTP)	TTP is calculated from the start date of induction therapy to the date of relapse/progression	Average time period between the start day of induction therapy and the day of relapse or progression	No
Primary	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	Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly	No
Primary	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.	Within 30 days after the last dose of study drug	Yes
Primary	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).	90 days after first ASCT	No
Primary	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).	90 days after second ASCT	No
Secondary	Overall survival (OS)	OS is measured from the start date of induction therapy until death from any cause	Average time period between the start day of induction therapy and the day of death, due to any cause	No
Secondary	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)	Average time period between the start day of induction therapy and the day of death, due to any cause	No
Secondary	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)	Average time period between the start day of induction therapy and the day of death, due to any cause	No
Secondary	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)	Average time period between the start day of induction therapy and the day of relapse or progression	No
Secondary	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)	Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly	No
Secondary	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)	Average time period between the start day of induction therapy and the day of relapse or progression	No
Secondary	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)	Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly	No