Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by PETHEMA Foundation
Sponsor:
Collaborators:
Janssen-Cilag Ltd.
Celgene Corporation
TFS Trial Form Support
Information provided by (Responsible Party):
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT01237249
First received: November 4, 2010
Last updated: April 14, 2014
Last verified: November 2013
  Purpose

This is a national, multicenter, open-label, randomized, comparative study designed to compare, first, the TTP of the two treatment schemes proposed (MPV followed by Rd or MPV alternating with Rd) in newly diagnosed MM patients older than 65 years. This comparison will be performing in terms of both efficacy and safety. Up to 120 patients will be included in each treatment arm and evaluated at scheduled visits in up to 3 study periods: Pre-treatment, Treatment and Follow-up.

Primary outcome measure:

  • To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.
  • To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd.

Secondary outcome measure:

  • To evaluate the response, duration of response, progression free survival (PFS), time to next therapy (TNT) and overall survival (OS) in the two different groups of patients.
  • To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments

Condition Intervention Phase
Multiple Myeloma
Drug: Melphalan
Drug: Prednisone
Drug: Velcade
Drug: Revlimid
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A National, Open-label, Multicenter, Randomized, Comparative Phase IIb Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone (Rd).

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd,in terms of adverse events presented in both groups of patients [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the response in both groups of patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Duration of response in two groups of patients [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) in two different groups of patients [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Time to next therapy (TNT) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) in the two different groups of patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: March 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MPV followed by Revlimid/Low Dose Dexamethasone (Rd)
Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)
Drug: Melphalan Drug: Prednisone Drug: Velcade
Experimental: Alternating MPV with Revlimid/Low Dose Dexamethasone
Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)
Drug: Revlimid Drug: Dexamethasone

Detailed Description:

The Pre-treatment period includes Screening visit. After providing written informed consent form to participate in the study, patients will be evaluated for eligibility during a screening period of 14 days (Days -14 to -1). If patients meet all inclusion and exclusion criteria will be randomized at the moment of entry in the trial in a 1:1 allocation to receive either MPV followed by Rd (Treatment Group A) or MPV alternating with Rd (Treatment Group B).

Patients in the Treatment Group A will receive nine cycles of MPV consisting on one 6-weeks cycle of Velcade (Bortezomib) as an intravenous bolus twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32) followed by a 10 day rest period (day 33 to 42), in combination with oral Melphalan, once daily on days 1 to 4 and oral Prednisone, once daily on days 1 to 4, followed by eight 4-weeks cycles of Velcade (Bortezomib) as an intravenous bolus on days 1, 8, 15 and 22 followed by a 6 day rest period (days 23 to 28), in combination with Melphalan and Prednisone per os once daily on days 1 to 4, followed by a 24-day rest period (days 5 to 28). After the nine MPV cycles, patients will receive nine cycles of Rd consisting on 4-weeks cycles, including Revlimid (lenalidomide), once daily on days 1-21 followed by a 7 day rest period (days 22 to 28) plus oral dexamethasone, once weekly on days 1,8,15 and 22, followed by a 6 day rest period (days 23 to 28).

Patients in the Treatment Group B will receive the same schedule of therapy, but the MPV cycles will be alternated with Rd cycles. In this treatment Group B, patients will be again randomized to start receiving either MPV or Rd as first cycle of therapy. Overall, patients will receive an identical number of cycles, nine cycles of MPV and nine of Rd. Patients randomized to Treatment Group A relapsing/progressing or with major toxicities under treatment with MPV will be crossover to receive Rd, but only after study coordinator approval.

During the Treatment Period, patients will be evaluated at day 1 of each cycle. After completion of the Treatment Period, all patients will be evaluated every 2 months thereafter.

Safety will be assessed by the monitoring of adverse events, physical examinations, vital signs measurements, and haematology and clinical chemistry test. Response to treatment will be based on EBMT an IMWG criteria. Response to treatment will be evaluated at day 1 of each induction cycle, and every 2 months during thereafter.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent obtained before starting any study-specific procedure.
  2. Symptomatic elderly MM newly diagnosed by EBMT criteria older than 65 years.
  3. Performance status (ECOG) ≤ 2.
  4. Have pre-treatment clinical laboratory values meeting the following criteria within 14 days of randomization:

    • platelet count ≥ 75x109/L
    • haemoglobin ≥ 8g/dL
    • absolute neutrophil count (ANC) ≥ 1.0x109/L
    • Serum bilirubin ≤ 1.5 mg/dL and alkaline phosphatise ≤ 2.5 x ULN AST, ALT ≤ 2.5 x ULN
    • Serum creatinine ≤2,5 mg/dl

Exclusion Criteria:

  1. Patient previously received treatment with Velcade or Revlimid.
  2. Patient previously received treatment for Multiple Myeloma.
  3. Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrolment.
  4. Patient has hypersensitivity to bortezomib, boron, mannitol or lenalidomide.
  5. Patient has received other investigational drugs with 28 days before enrolment.
  6. Patient had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  7. Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
  8. Radiation therapy within 30 days before randomization, at least patient has had antialgic radiation. Radiation therapy will be afterwards permitted during the treatment period if it is indicated due to the presence of plasmacytomas
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237249

Contacts
Contact: Bladé Joan, Dr 34 93 227 54 00 jblade@clinic.ub.es

  Show 63 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
Janssen-Cilag Ltd.
Celgene Corporation
TFS Trial Form Support
  More Information

Additional Information:
No publications provided

Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT01237249     History of Changes
Other Study ID Numbers: GEM2010MAS65
Study First Received: November 4, 2010
Last Updated: April 14, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Multiple Myeloma
Velcade
Revlimid

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
Bortezomib
Lenalidomide
Melphalan
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014