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NCT Number: NCT01341262

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

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.

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Key information

Conditions

Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

thalidomide

Drug
  • 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

Drug
  • 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

Drug
  • 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

Drug

Cyclophosphamide 7 g/sqm + G-CSF 5 mcg/Kg from the day +6 for stem cell mobilisation

melphalan

Drug

Melphalan 200 mg/sqm on day -1 for first and second ASCT

Primary outcomes

  1. Response rate (at least PR, VGPR, nCR and CR) to thal-dex induction

    Time frame: 120 days after the start day of tal-dex induction therapy

    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).

  2. duration of response (partial response, PR, very good partial response, VGPR, complete response, CR)

    Time frame: Average time period between the day of first achievement of response and the day of first relapse or progression

    Duration of response is calculated from the first achievement of the response (at least PR, at least VGPR, at least CR) to relapse/progression

  3. time to progression (TTP)

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression

    TTP is calculated from the start date of induction therapy to the date of relapse/progression

  4. progression free survival (PFS)

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly

    PFS is calculated from the start date of induction therapy to the date of relapse/progression or death for any cause, whichever occurs first

  5. toxicity of thal-dex (induction and subsequent treatment phases)

    Time frame: Within 30 days after the last dose of study drug

    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.

  6. Response rate (at least PR, VGPR, nCR and CR) to first ASCT

    Time frame: 90 days after 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).

  7. Response rate (at least PR, VGPR, nCR and CR) to second ASCT

    Time frame: 90 days after 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 outcomes

  1. Overall survival (OS)

    Time frame: Average time period between the start day of induction therapy and the day of death, due to any cause

    OS is measured from the start date of induction therapy until death from any cause

  2. OS by cytogenetic abnormalities

    Time frame: Average time period between the start day of induction therapy and the day of death, due to any cause

    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)

  3. OS by 18F-FDG PET/CT imaging

    Time frame: Average time period between the start day of induction therapy and the day of death, due to any cause

    OS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)

  4. TTP by cytogenetic abnormalities

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression

    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)

  5. PFS by cytogenetic abnormalities

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly

    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)

  6. TTP by 18F-FDG PET/CT imaging

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression

    TTP is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)

  7. PFS by 18F-FDG PET/CT imaging

    Time frame: Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly

    PFS is calculated as defined above in patients with different PET/CT patterns (normal, focal, diffuse, presence or absence of extramedullary disease)

Sponsors and collaborators

Lead sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Other

Registry information

Official study title

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

Important dates

Study start
2002
Primary completion
2007
Study completion
2009
First posted
Apr 25, 2011
Registry last updated
Apr 25, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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