Melphalan, Prednisone, and CC-5013 (Revlimid) as Induction Therapy in Multiple Myeloma

NCT ID: NCT00396045

Last Updated: 2006-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2008-01-31

Brief Summary

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The purpose of this study is to evaluate the safety and efficacy of the association of Melphalan/Prednisone/Revlimid (MPR) as induction treatment for newly diagnosed myeloma patients over age 65 or those under 65 years who refuse or are not eligible for high dose therapy. This association might further increase the response rate achieved by the standard oral MP regimen.

Detailed Description

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In Multiple Myeloma patients, the standard treatment is the oral combination of Melphalan and Prednisone (MP). This approach induces a partial response (PR) rate of approximately 50% and a complete remission (CR) rate of 1-5%, with a median remission duration of 18-20 months and a median overall survival of 3 years.

Recently, the combination of oral MP plus thalidomide increased response rate to 80% and complete remission rate to 20%, marked cytoreduction is the first step toward a sustained remission period.

CC-5013 (Revlimid) is a thalidomide analogue, 50000 times more potent than thalidomide in inhibiting TNF-alfa secretion, a potent growth factor for myeloma cells. Revlimid represents a novel class of anti-cancer drugs, it is active in patients with multiple myeloma who are refractory to conventional and high-dose chemotherapy with a response rate of approximately 30%. The association Revlimid plus dexamethasone further increases the response rate induced by Revlimid by an additional 30%.

This study will evaluate the safety and efficacy of the association of Melphalan/Prednisone/Revlimid (MPR) as induction treatment for newly diagnosed myeloma patients over age 65 or those under 65 years who refuse or are not eligible for high dose therapy. This association might further increase the response rate achieved by the standard oral MP regimen.

In the first part of the study (phase I component), different doses of oral Melphalan (0.18-0.25 mg/Kg) associated with Prednisone (MP) will be combined with escalating doses of Revlimid (from 5 mg/day) and administered together. This phase will define the MTD of the association. In the second part of the study (phase II component), 30 patients will be treated with MPR at dose/s defined from phase I component to verify data of response and toxicity.

Conditions

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Multiple Myeloma

Keywords

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Multiple Myeloma, Lenalidomide, elderly patients

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Revlimid (CC-5013)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient is of a legally consenting age as defined by local regulations.
* Age \> 65 years or age \< 65 years in patients who refuse or are not eligible for high-dose therapy.
* Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method)(Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of Lenalomide therapy - Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of Lenalomide therapy.
* Patient was previously diagnosed with symptomatic multiple myeloma based on standard criteria, and has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of \>200 mg/24 hours; measurable plasmacytoma as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells \>10%.
* Patient has a Karnofsky performance status ≥ 60%
* Patient has a life-expectancy \> 6 months.
* Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):
* Absolute neutrophil count \> 1.5 x 109/L without the use of growth factors
* Platelet count \> 75 x 109/L without transfusion support within 7 days before the test.
* Calculated or measured creatinine clearance: ≥ 20 mL/minute
* Total bilirubin \< 1.5 x the ULN
* AST (SGOT) and ALT (SGPT) \< 2.5 x ULN
* Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L

Exclusion Criteria

* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
* Pregnant or beast feeding females.
* Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
* Use of any other concomitant standard/experimental anti-myeloma drug or therapy.
* Any prior use of CC-5013 or other anti-myeloma therapy.
* Any of the following laboratory abnormalities:
* Platelet count \< 75 x 109/L.
* Absolute neutrophil count \<1.5 x 109/L.
* Calculated or measured creatinine clearance \<20 mL/minute.
* Corrected serum calcium \>14 mg/dL (3.5 mmol/L).
* Aspartate transaminase (AST): \>2.5 x the upper limit of normal (ULN).
* Alanine transaminase (AST): \> 2.5 x the ULN.
* Total bilirubin: \> 1.5 x the ULN.
* Known positive for HIV or active infectious hepatitis, type B or C.
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Turin, Italy

OTHER

Sponsor Role lead

Principal Investigators

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MARIO BOCCADORO, MD

Role: PRINCIPAL_INVESTIGATOR

DIVISIONE DI EMATOLOGIA DELL'UNIVERSITA' DI TORINO, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY

ANTONIO PALUMBO, MD

Role: STUDY_DIRECTOR

DIVISIONE UNIVERSITARIA DI EMATOLOGIA, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY

Locations

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Unità Operativa di Ematologia, Spedali Civili

Brescia, Brescia, Italy

Site Status

Reparto di Ematologia, Ospedale Ferrarotto

Catania, Catania, Italy

Site Status

Unità Operativa Complessa Di Ematologia, Presidio Ospedaliero Dell'Annunziata, Azienda Ospedaliera Di Cosenza

Cosenza, COSENZA, Italy

Site Status

Unità Operativa di Ematologia Trapianto di Cellule Staminali, Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Site Status

Clinica Ematologica, Ospedale San Martino -Università di Genova

Genova, Genova, Italy

Site Status

Cattedra di Ematologia, Dipart. Di Medicina Interna e Scienze Biomediche

Parma, Parma, Italy

Site Status

Divisione di Ematologia-Policlinico Umberto I-Università La Sapienza

Roma, Roma, Italy

Site Status

Divisione di Ematologia, Azienda Ospedaliera Senese Ospedale A. Sclavo

Siena, Siena, Italy

Site Status

Div. Univ. Di Ematologia, Az. Osp. San Giovanni Battista

Torino, TORINO, Italy

Site Status

Countries

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Italy

References

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Palumbo A, Bertola A, Musto P, Caravita T, Callea V, Nunzi M, Grasso M, Falco P, Cangialosi C, Boccadoro M. Oral melphalan, prednisone, and thalidomide for newly diagnosed patients with myeloma. Cancer. 2005 Oct 1;104(7):1428-33. doi: 10.1002/cncr.21342.

Reference Type BACKGROUND
PMID: 16116606 (View on PubMed)

Dimopoulos MA, Anagnostopoulos A, Weber D. Treatment of plasma cell dyscrasias with thalidomide and its derivatives. J Clin Oncol. 2003 Dec 1;21(23):4444-54. doi: 10.1200/JCO.2003.07.200.

Reference Type BACKGROUND
PMID: 14645435 (View on PubMed)

Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F, LeBlanc R, Catley LP, Doss D, Kelly K, McKenney M, Mechlowicz J, Freeman A, Deocampo R, Rich R, Ryoo JJ, Chauhan D, Balinski K, Zeldis J, Anderson KC. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood. 2002 Nov 1;100(9):3063-7. doi: 10.1182/blood-2002-03-0996.

Reference Type BACKGROUND
PMID: 12384400 (View on PubMed)

Kraut EH, Crowley JJ, Wade JL, Laufman LR, Alsina M, Taylor SA, Salmon SE. Evaluation of topotecan in resistant and relapsing multiple myeloma: a Southwest Oncology Group study. J Clin Oncol. 1998 Feb;16(2):589-92. doi: 10.1200/JCO.1998.16.2.589.

Reference Type BACKGROUND
PMID: 9469346 (View on PubMed)

Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. doi: 10.1046/j.1365-2141.1998.00930.x. No abstract available.

Reference Type BACKGROUND
PMID: 9753033 (View on PubMed)

Other Identifiers

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MPR

Identifier Type: -

Identifier Source: secondary_id

RV-MM-PI-026

Identifier Type: -

Identifier Source: org_study_id