Iberoamerican Protocol With Thalidomide in Patients With Symptomatic Newly Diagnosed Multiple Myeloma Over 65 Years

NCT ID: NCT01532856

Last Updated: 2012-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2012-06-30

Brief Summary

This protocol is an international, multicenter, comparative, open and randomized study designed to compare the safety and efficacy (in terms of response rate) from three induction chemotherapy schemes -Thalidomide/Cyclophosphamide/Dexamethasone versus Thalidomide/Dexamethasone versus Thalidomide/Melphalan/Prednisone. Finally, this study is also designed to compare the safety and efficacy (in terms of duration of response) of two maintenance chemotherapy regimens - Thalidomide/Prednisone versus Thalidomide. Each treatment arm will include 100 patients and assessments and scheduled visits will be conducted in three periods: Pre-treatment, treatment and monitoring. Security will be evaluated by monitoring all adverse events, physical examination, vital signs and biochemical studies. Response to treatment will be evaluated according to the EBMT21 criteria and will be assessed on day 1 of each cycle of induction, at the end of nine cycles of induction therapy and monthly during the first year of maintenance therapy and every 3 months thereafter.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A induction therapy

Thalidomide + Cyclophosphamide + Dexamethasone

Group Type: ACTIVE_COMPARATOR

Thalidomide, Cyclophosphamide, Dexamethasone

Intervention Type: DRUG

Thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle Cyclophosphamide - 50mg per day, orally, during 9 cycles of 28 days each cycle Dexamethasone - 40mg orally(two pulses the first two cycles in days 1-4 and 15-18 and then a single pulse in each other cycle) during 9 cycles of 28 days.

Group B induction therapy

thalidomide + dexamethasone

Group Type: ACTIVE_COMPARATOR

Thalidomide, Dexamethasone

Intervention Type: DRUG

Thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle Dexamethasone - 40mg orally, in three pulses (days 1 to 4, 9 to 12 and 17 20) odd cycles and a single pulse treatment in pairs cycles, during 9 cycles of 28 days each cycle

Group C induction therapy

thalidomide + melphalan + prednisone

Group Type: ACTIVE_COMPARATOR

Thalidomide, Melphalan, Prednisone

Intervention Type: DRUG

thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle; melphalan - 4 mg/m2, days 1-7, orally, during 9 cycles of 28 days each cycle; prednisone - 40 mg/m2, days 1-7, orally, during 9 cycles of 28 days each cycle

Interventions

Thalidomide, Cyclophosphamide, Dexamethasone

Thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle Cyclophosphamide - 50mg per day, orally, during 9 cycles of 28 days each cycle Dexamethasone - 40mg orally(two pulses the first two cycles in days 1-4 and 15-18 and then a single pulse in each other cycle) during 9 cycles of 28 days.

Intervention Type: DRUG

Thalidomide, Dexamethasone

Thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle Dexamethasone - 40mg orally, in three pulses (days 1 to 4, 9 to 12 and 17 20) odd cycles and a single pulse treatment in pairs cycles, during 9 cycles of 28 days each cycle

Intervention Type: DRUG

Thalidomide, Melphalan, Prednisone

thalidomide - 200mg per day, orally, during 9 cycles of 28 days each cycle; melphalan - 4 mg/m2, days 1-7, orally, during 9 cycles of 28 days each cycle; prednisone - 40 mg/m2, days 1-7, orally, during 9 cycles of 28 days each cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• > 65 years old and non candidate for autologous stem cell transplant
• Patient must be newly diagnosed with Multiple Myeloma according to establish criteria symptoms. Steroid pulses administration are allowed for any required emergency prior to starting induction therapy or bisphosphonates administration
• Patient must have measurable disease, defined as follows: for secretory multiple myeloma, measurable disease is defined by the presence of measurable monoclonal component in serum or in urine excretion if light chain is greater than or equal to 200 mg/24 hours(Annex 5)
• Measured ECOG < 2 state level.
• The patient must have a life expectancy greater than 3 months.
• Adequate laboratory values prior to induction treatment initiation, defined as follow:

1. Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g / dl and absolute neutrophil count ≥ 1000/mm3. Lower values are permitted if they are due to BM infiltration.

2. Corrected serum calcium ≤ 14mg/dl.

3. Aspartate transaminase (AST): ≤ 2.5 x normal upper limit.

4. Alanine transaminase (ALT):): ≤ 2.5 x normal upper limit.

5. Total bilirubin: ≤ 1.5 x normal upper limit.

6. Serum creatinine ≤ 2 mg / dl.

• Men (including vasectomy done) must use barrier contraception (latex condoms) when having sex with women of potential childbearing, and for at least four weeks after thalidomide last dose.

Exclusion Criteria

• Non-secretory MM.
• Previous treatment for multiple myeloma with the exception of steroid pulses for any emergency that requires treatment before beginning the induction, administration of bisphosphonates or radiation therapy.
• Basal peripheral neuropathy higher than grade 2 within 14 days of inclusion.
• Known thalidomide hypersensitivity.
• Use of any investigational agent within 30 days prior to their inclusion.
• Known human immunodeficiency virus(HIV) infection, detectable surface antigen of hepatitis B or active infection by the hepatitis C viruses
• Myocardial infarction within 6 months prior to inclusion or heart functional class III or IV according to New York Heart Association (NYHA) heart failure, angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram or conduction system abnormalities.
• Participation in another clinical trial or receiving any investigational agent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo de Estudos Multicentricos em Onco-Hematologia

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vania Hungria, PhD MD

Role: PRINCIPAL_INVESTIGATOR

Santa Casa de Misericordia de São Paulo

Locations

Hospital Universitário Clementino Fraga Filho

Rio de Janeiro, Rio de Janeiro, Brazil

Universidade Federal do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, Brazil

Santa Casa de Misericórdia de São Paulo

São Paulo, São Paulo, Brazil

Countries

Brazil

Other Identifiers

GBRAM0002

Identifier Type: -

Identifier Source: org_study_id