Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients

Browse trials for

• Multiple Myeloma 3,632
• Neoplasms, Plasma Cell 2,306

Keywords

• Treatment for patients with multiple myeloma
• who have received no prior treatment

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 158 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Lead sponsor

Millennium Pharmaceuticals, Inc. is the lead sponsor of 173 studies on the registry; none are open to participants now.

Of its 73 completed or terminated interventional studies of FDA-regulated products, 72 (99%) have results posted.

Study arms

• Experimental
  VDR

  VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)

  Drug: VELCADE (bortezomib) · Drug: dexamethasone · Drug: Revlimid (lenalidomide)

• Experimental
  VDCR

  VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)

  Drug: VELCADE (bortezomib) · Drug: dexamethasone · Drug: cyclophosphamide · Drug: Revlimid (lenalidomide)

• Experimental
  VDC

  VELCADE (bortezomib), dexamethasone, cyclophosphamide

  Drug: VELCADE (bortezomib) · Drug: dexamethasone · Drug: cyclophosphamide

• Experimental
  VDC-mod

  Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide

  Drug: VELCADE (bortezomib) · Drug: dexamethasone · Drug: cyclophosphamide

Interventions

• DrugVELCADE (bortezomib)

  bortezomib 1.3 mg/m\^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).

• Drugdexamethasone

  dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop

• Drugcyclophosphamide

  cyclophosphamide 500 mg/m\^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

• DrugRevlimid (lenalidomide)

  lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm) lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)

Primary outcomes

1. Number of Patients With Combined Complete Response and Very Good Partial Response

   Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. Very good partial response requires serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h

   Time frame: Up to 48 weeks or until disease progression

Secondary outcomes

1. Number of Patients With Adverse Events (AEs)

   Evaluate the safety and tolerability of the combination therapy

   Time frame: From first dose of study drug through the 30 day post-treatment AE assessment visit

2. Number of Patients With Overall Response

   Overall Response includes complete response and partial response. Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to \< 200 mg per 24 hour.

   Time frame: Up to 48 weeks or until disease progression

3. Number of Patients With Stringent Complete Response Rate

   Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

   Time frame: Up to 48 weeks or until disease progression

4. Number of Patients With Complete Response Rate + Near Complete Response Rate

   Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow.

   Time frame: Up to 48 weeks or until disease progression

5. Duration of Response

   Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments. Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

   Time frame: Up to 48 weeks or until disease progression

6. Time to Disease Progression

   Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease. Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

   Time frame: Up to 48 weeks or until disease progression

7. Time to Response

   Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments.

   Time frame: Up to 48 weeks or until disease response

8. Progression-free Survival

   Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death. Disease progression requires any one or more of the following: serum m-protein increase \>= 25% from nadir(absolute increase \>= 0.5 g/dL); Urine m-protein increase \>= 25% from nadir(absolute increase \>= 200 mg/24 hr), bone marrow plasma cell percentage increase \>= 25% from nadir(absolute increase \>= 10%), new bone lesion or soft tissue plasmacytomas.

   Time frame: Up to 48 weeks or until disease progression/death

9. Probability of 1-year Survival

   Time frame: survival probability at 1 year after randomization

10. Overall Survival

    Overall survival is defined as time from the date of randomization to the date of death

    Time frame: Up to 48 weeks or until death

Baseline characteristics

Publications

• Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. doi: 10.1182/blood-2011-11-395749. Epub 2012 Mar 15. PubMed 22422823 ↗
• Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N, Bhandari M, Wolf JL, Gasparetto C, Krishnan A, Grosman D, Glass J, Sahovic EA, Shi H, Webb IJ, Richardson PG, Rajkumar SV. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia. 2010 Jul;24(7):1350-6. doi: 10.1038/leu.2010.116. Epub 2010 May 27. PubMed 20508619 ↗