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

PETHEMA Foundation

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Thalidomide/Dexamethasone; Drug: VBMCP/VBAD/Velcade; Drug: Velcade/Thalidomide/Dexamethasone

Study type: Interventional

Funder types: Other

Identifiers

NCT00461747

2005-001110-41

Details and patient eligibility

About

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.

Full 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.

Enrollment: 390 estimated patients

Sex: All

Ages: Under 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 3 patient groups

A

Active Comparator group

Description:

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

Treatment:

Drug: VBMCP/VBAD/Velcade

B

Experimental group

Description:

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

Treatment:

Drug: Thalidomide/Dexamethasone

C

Experimental group

Description:

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.

Treatment:

Drug: Velcade/Thalidomide/Dexamethasone