GEM05 for Patients With Multiple Myeloma Under 65 Years (GEM05MENOS65)

This study has been completed.
Sponsor:
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00461747
First received: April 17, 2007
Last updated: September 17, 2009
Last verified: September 2009
  Purpose

The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone. The second one is to evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide versus Thalidomide/Velcade.


Condition Intervention Phase
Multiple Myeloma
Drug: VBMCP/VBAD/Velcade
Drug: Thalidomide/Dexamethasone
Drug: Velcade/Thalidomide/Dexamethasone
Phase 3

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 III Study of Induction Treatment With VBMCP-VBAD/Velcade Versus Thalidomide / Dexamethasone Versus Velcade / Thalidomide / Dexamethasone Followed by High Dose Intensive Therapy With Autologous Hemopoietic Stem Cell Support and Maintenance Treatment With Interferon-a Versus Thalidomide Versus Thalidomide / Velcade in Untreated Patients With Multiple Myeloma Less Than 65 Yrs Old

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 390
Study Start Date: March 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A

Four alternating cycles of VBMCP/VBAD + Velcade VBMCP: Vincristine, 0,03 mg/Kg (iv) day 1, BCNU, 0,5 mg/Kg iv day 1, Cyclophosphamide, 10 mg/Kg iv day 1, Melfalán, 0,25 mg/Kg oral days 1 to 4 Prednisone, 1 mg/Kg oral days 1 to 4; 0,5 mg/Kg oral days 5 to 8 and 0,25 mg/Kg oral days 9 to 12.

VBAD : Vincristine, 1mg via iv day 1, BCNU, 30 mg/m2 iv day 1, Adriamycine, 40mg/m2 iv day 1 Dexamethasone, 40 mg oral days 1 to 4, 9 to 12 and 17 to 20. The interval between VBMCP and VBAD is 5 weeks and between VBAD and VBMCP is 4 weeks. The patients will received two cycles of VBMCP and two cycles of VBAD. After 4 weeks of last cycle of VBAD, patients will received two cycles of Velcade, 1,3 mg/ m2 iv twice a week (days 1, 4, 8 and 11), followed by 10 days without treatment

Drug: VBMCP/VBAD/Velcade

VBMCP: Vincristine, 0,03 mg/Kg (iv) day 1, BCNU, 0,5 mg/Kg iv day 1, Cyclophosphamide, 10 mg/Kg iv day 1, Melfalan, 0,25 mg/Kg oral days 1 to 4 Prednisone, 1 mg/Kg oral days 1 to 4; 0,5 mg/Kg oral days 5 to 8 and 0,25 mg/Kg oral days 9 to 12.

VBAD : Vincristine, 1mg via iv day 1, BCNU, 30 mg/m2 iv day 1, Adriamycine, 40mg/m2 iv day 1 Dexamethasone, 40 mg oral days 1 to 4, 9 to 12 and 17 to 20.

Experimental: B

Six cycles of 4 weeks of Thalidomide/Dexamethasone. Thalidomide day 1, cycle 1 (50 mg/day v.o). If toxicity < grade 2, dose will be 100 mg/day on day 15, cycle 1 and 200 mg/day on day 1, cycle 2.

Dexamethasone:40 mg/day v.o.days 1 to 4 and 9 to 12, with a period without treatment of 16 days

Drug: Thalidomide/Dexamethasone

Thalidomide day 1, cycle 1 (50 mg/day v.o). If toxicity < grade 2, dose will be 100 mg/day on day 15, cycle 1 and 200 mg/day on day 1, cycle 2.

Dexamethasone:40 mg/day v.o.days 1 to 4 and 9 to 12, with a period without treatment of 16 days

Experimental: C

Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is < grade 2, the dose will be increased (100 mg/day) at day 15 cycle 1 and (200 mg de Thalidomide) at day 1 cycle 2.

Dexamethasone: 40 mg/day v.o days 1 to 4 and 8 to 11, with a period without treatment of 17 days.

Velcade: 1,3 mg/m2 iv twice a week (days 1, 4, 8 and 11) with a period without treatment of 17 days.

Drug: Velcade/Thalidomide/Dexamethasone

Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is < grade 2, the dose increased (100 mg/day) at day 15 cycle 1 and (200 mg de Thalidomide) at day 1 cycle 2.

Dexamethasone: 40 mg/day v.o days 1 to 4 and 8 to 11, with a period without treatment of 17 days.

Velcade: 1,3 mg/m2 iv twice a week (days 1, 4, 8 and 11) with a period without treatment of 17 days


Detailed Description:

A total of up to 390 patients ≤ 65 years old diagnosed of Multiple Myeloma with symptomatic disease and that have not received previous chemotherapy for MM will be included.

Patients will be evaluated at scheduled visits in up to three study periods: Pre-treatment, Treatment and Follow up.

The Pre-treatment includes Screening and baseline visits. After providing informed consent, patients will be evaluated for study eligibility and then Patients will be randomized (1:1:1) to receive VBMCP-VBAD+Velcade (Group A) or Thalidomide+Dexamethasone (Group B) or Thalidomide+Dexamethasone+Velcade (Group C). All of them will received the induction treatment up to 24 weeks.

After 4 weeks, without progression or unacceptable toxicity, There will be stem cell mobilization to do an autologous transplant. Three months after transplant, patients will be again randomized (1:1:1) to receive maintenance treatment: Interferon-a (Group M1) or Thalidomide (Group M2) or Thalidomide+Velcade (Group M3) during three years.

Once the treatment period has finished a follow up will be carry out. During this period we will evaluated response, progression-free survival and global survival every three months.

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must be able to comply with the protocol requirements
  2. Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care,
  3. Age <65 years and possibly to do an autologous transplant.
  4. Patient recently diagnosed with symptomatic Multiple Myeloma who has not received any previous chemotherapy treatment for Multiple Myeloma.
  5. Patient has a measurable disease defined as quantifiable serum monoclonal protein value and, where applicable, urine Light-chain excretion of ≥ 200 mg/24 hours.
  6. ECOG < 2.
  7. El patient has a life-expectancy > 3 months.
  8. Patient has the following laboratory values before beginning induction treatment:

    1. Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed if they are due to marrow infiltration.
    2. Corrected serum calcium <14mg/dl.
    3. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
    4. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal.
    5. Total bilirubin: ≤1.5 x the upper limit of normal.
    6. Serum creatinine ≤ 2 mg/dl.
  9. For Patients included in Thalidomide branches: women of childbearing age must not have sex unless they use two anticonceptive methods beginning 4 weeks before the first dose, during all the study until 4 weeks after the last one.

Exclusion Criteria:

  1. Non-secretor Myeloma.
  2. Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates or radiotherapy before beginning treatment.
  3. Patients with < Grade 2 peripheral neuropathy within 14 days before enrolment.
  4. Patient had major surgery within 4 weeks before enrolment.
  5. Patient has hypersensitivity to bortezomib, boron or mannitol or Thalidomide.
  6. Patient has received other investigational drugs within 30 days before enrolment.
  7. Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
  8. Patient had a myocardial infarction within 6 months of enrollment 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.
  9. Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
  10. Pregnancy or breast-feed women.
  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: NCT00461747

  Show 79 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Principal Investigator: Bladé Joan, Dr Hospital Clinic of Barcelona
  More Information

Additional Information:
Publications:
1. Greenlee RT, Murray T, Bolden S , Wingo PA. Cancer Statistics, 2000. CA Cancer J Clin, 2000; 50: 7-33.
2. Longo D. Plasma cell disorders. In : Fauce A, et al. Ed. Harrison's Principles of Internal Medicine. 14th Ed. New York, New York: Mc Graw-Hill; 1998: 712-718
23. Barlogie B, Ayers D, Spoon D, et al. Towards curing myeloma. durable CR in the absence of chromosome 13 deletion and with timely application of two cycles of melphalan-based high dose therapy. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 49.
Alexanian R, Weber D, Delasalle K, Dimopoulos M, Giralt S, Champlin R. Early myeloablative therapy with autologous stem cells for multiple myeloma in remission with primary therapy. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 61.
25. Bladé J, Esteve J, Rives S, et al. Early autologous stem cell transplantation versus standard chemotherapy after first response in multipple myeloma: a report of a non-randomized study from a single institution. Proceedings of the VII International Multiple Myeloma Workshop, Stockholm, September 1999, pp: 148.
34. Singhal S, Mehta J., Desikan R., Ayers D., Roberson P., Eddlemon P., Munshi N., Anaissie E., Wilson C., Dhodapkar M., Zeldis J., Barlogie B. Antitumor Activity of Thalidomide in Refractory Multiple Myeloma. NEJM 1999; 341:1565-71.
35. Singhal S, Mehta J., Eddlemon P., Gray P., Cromer J., Desikan R., Ayers D., Siegel D., Munshi N., Anaissie E., Kantarjian H., Zeldis J., Barlogie B. Marked anti-tumor effect from anti-angiogenesis therapy with thalidomide in high risk refractory multiple myeloma. Blood, 1998; 92(suppl 1):318a (abstract).
38. Rajkumar S, Blood E, Vesole D, Shepard R, Greipp P. Thalidomide plus dexamethasone versus dexamethasone alone in newly diagnosed multiple myeloma. Blood 2004. Volume 104, issue 11. Abstract 205
41. Paul Richardson et al. Bortezomib Demonstrates Superior Efficacy to High-Dose Dexamethasone in Relapsed Multiple Myeloma: Final Report of the APEX Study. Blood 2004; 104(11):Abstract number 336.5
42. Maurizio Zangari, Bart Barlogie, Joth Jacobson, Erik Rasmussen, Michael Burns, Bob Kordsmeier, John D. Shaughnessy, Elias J. Anaissie, Raymond Thertulien, Athanasios Fassas, Choon-Kee Lee, David Schenkein, Jerome B. Zeldis, Guido Tricot. VTD Regimen Comprising Velcade (V) + Thalidomide (T) and Added DEX (D) for Non-Responders to V + T Effects a 57% PR Rate among 56 Patients with Myeloma (M) Relapsing after Autologous Transplant. Blood 2003, Volume 102, issue 11. Abstract number 830
43. Jagannath S, Brian D, Wolf j, Camacho E, Irwin D, Lutzky J, Mckinley M, Gabayan E, Mazumder A, Crowley K, Sckenkein D. A phase 2 study of Bortezomib as first-line therapy in patients with multiple myeloma. Blood 2004; 104(11). Abstract number 333
44. Alexanian R, Wang L, Weber D, Delasalle K. VTD (Velcade, Thalidomide, Dexamethasone) as primary therapy for newly-diagnosed multiple myeloma. Blood 2004; 104(11). Abstract number 210
46. Whealthy K (On behalf of the Myeloma Trialists`Collaborative Group). Which myeloma patients benefit from interferon therapy? An overview of 24 randomised trials with 4,000 patients, Br J Haematol 1998; 102: 140.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: pethema
ClinicalTrials.gov Identifier: NCT00461747     History of Changes
Other Study ID Numbers: 2005-001110-41
Study First Received: April 17, 2007
Last Updated: September 17, 2009
Health Authority: Spain:Spanish Ministry of Health

Keywords provided by PETHEMA Foundation:
Untreated
Transplant
Younger

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
Dexamethasone 21-phosphate
Bortezomib
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014