Melphalan, Prednisone, Thalidomide and Defibrotide in Relapsed Multiple Myeloma Patients

NCT00406978 | Completed Phase 1

• 1 other identifier: MM2005
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

This study will evaluate the safety and the efficacy of the association of Melphalan/ Prednisone/Thalidomide/Defibrotide (MPTD) as salvage treatment in advanced and refractory myeloma patients. This association might further increase the response rate achieved by oral MPT regimen

Conditions

Multiple Myeloma

Keywords

MYELOMA; THALIDOMIDE; DEFIBRODITE

Outcome Measures

Primary Outcomes (2)

• The safety will be assessed by showing DLT and maximum tolerated dose (MTD) of defibrotide when administered in combination with MPT

  The DLT is defined by the development of febrile neutropenia, or Grade 4 neutropenia \>= a week, or Grade 4 hematologic toxicity except neutropenia, or any \>= Grade 3 non-hematologic toxicity considered by investigators to be related to study drug(s) in \>30% of pts. MTD: maximum tolerated dose

  7 months

• The efficacy will be assessed by showing at least 55% of patients in a minimal response (MR) or at least 10 % of pts in near complete remission (nCR).

  7 months

Secondary Outcomes (3)

• prolongation of progression-free survival

  it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

• duration of progression-free survival

  it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

• prolongs overall survival

  it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

Study Arms (1)

MPTD

EXPERIMENTAL

Drug: Prednisone; Drug: Melphalan; Drug: Thalidomide; Drug: Defibrotide

Interventions

Prednisone DRUG

Prednisone will be given orally at the dose of 1.5 mg/Kg for 4 days followed by a 31-day rest period (days 5 through 35)

MPTD

Melphalan DRUG

Melphalan will be given orally at the dose of 0.25 mg/Kg for 4 days,

MPTD

Thalidomide DRUG

Thalidomide will be administered orally at the initial dose of 50 mg/day p.o. once daily, with increment of 50 mg after a month to acceptable tolerance (maximum 100 mg), continuously for the entire 6 courses.

MPTD

Defibrotide DRUG

Lev - 1 Def = 10 mg/Kg (max 0.6 g) on days 1-4, followed by 1.2 g (400 mg every 8 hours) p.o. through day 35 Lev - 1 Def = 1.2 g p.o (400 mg every 8 hours) on days 1-4, followed by 1.2 g (400 mg every 8 hours) p.o. through day 35 Level + 1 Def = 17 mg/Kg (max 1.2 g) on days 1-4, followed by 1.6 g p.o. (400 mg every 6 hours) through day 35 Lev + 1 Def = 2.4 g p.o. (400 mg every 4 hours) on days 1-4, followed by 1.6 g p.o. (400 mg every 6 hours) through day 35 Lev + 2 Def = 34 mg/Kg (max 2.4 g) as a i.v. injection on days 1-4, followed by 3.2 g p.o. (800 mg every 6 hours) through day 35 Lev + 2 Def = 4.8 g p.o. (800 mg every 4 hours) on days 1-4, followed by 3.2 g p.o. (800 mg every 6 hours) through day 35 Lev + 3 Def = 51mg/Kg (max 3.6 g) as a i.v. injection on days 1-4, followed by 4.8 g p.o. (1200 mg every 6 hours) through day 35 Lev + 3 Def = 7.2 g p.o.(1200 mg every 4 hours ) on days 1-4, followed by 4.8 g p.o. (1200 mg every 6 hours) given p.o. through day 35

MPTD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is of a legally consenting age as defined by local regulations.
• 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 or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
• Patient was previously diagnosed with multiple myeloma based on standard criteria (see Section 13.2).
• Patient is relapsed after one line of treatment but less than three lines, including high-dose chemotherapy with stem cell support, conventional poli-chemotherapy, thalidomide- and melphalan-based regimens
• Patient with primary refractory disease will be considered not eligible
• Patient 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.
• Patient has a Karnofsky performance status ≥60%.
• Patient has a life-expectancy \>3 months.
• Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration):
• Platelet count ≥90 x 109/L without transfusion support within 7 days before the test.
• Absolute neutrophil count (ANC) ≥ 1.00 x 109/L without the use of growth factors
• Corrected serum calcium ≤14 mg/dL (3.5 mmol/L).

You may not qualify if:

• 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
• Known positive for HIV or active infectious hepatitis, type B or C
• Other concurrent anticoagulation treatment

Sponsors & Collaborators

• Silvio Aime: lead

Study Sites (5)

Dip. Scienze Mediche & IRCAD-Università, UDA Ematologia

Novara, Novara, 28100, Italy

Location

Policlinico Monteluce, Clinica Medica I

Perugia, Perugia, 06123, Italy

Location

Divisione Di Ematologia, Ospedali Riuniti

Reggio Calabria, Reggio Calabria, Italy

Location

Servizio di Ematologia, Azienda Ospedaliera S. Maria Nuova

Reggio Emilia, Reggio Emilia, 42100, Italy

Location

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

Torino, TO, 10126, Italy

Location

Related Publications (6)

• Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol. 1988 May;6(5):889-905. doi: 10.1200/JCO.1988.6.5.889.

  PMID: 2452861 BACKGROUND

• Palumbo A, Bertola A, Falco P, Rosato R, Cavallo F, Giaccone L, Bringhen S, Musto P, Pregno P, Caravita T, Ciccone G, Boccadoro M. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J. 2004;5(4):318-24. doi: 10.1038/sj.thj.6200403.

  PMID: 15297848 BACKGROUND

• 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.

  PMID: 9753033 BACKGROUND

• McKean-Cowdin R, Feigelson HS, Ross RK, Pike MC, Henderson BE. Declining cancer rates in the 1990s. J Clin Oncol. 2000 Jun;18(11):2258-68. doi: 10.1200/JCO.2000.18.11.2258.

  PMID: 10829046 BACKGROUND

• Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.

  PMID: 2301376 BACKGROUND

• Palumbo A, Larocca A, Genuardi M, Kotwica K, Gay F, Rossi D, Benevolo G, Magarotto V, Cavallo F, Bringhen S, Rus C, Masini L, Iacobelli M, Gaidano G, Mitsiades C, Anderson K, Boccadoro M, Richardson P; Italian Multiple Myeloma Network GIMEMA. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial. Haematologica. 2010 Jul;95(7):1144-9. doi: 10.3324/haematol.2009.017913. Epub 2010 Jan 6.

  PMID: 20053869 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Prednisone; Melphalan; Thalidomide; defibrotide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• MARIO BOCCADORO, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 30, 2006
• First Posted: December 4, 2006
• Study Start: February 1, 2006
• Primary Completion: September 1, 2010
• Study Completion: April 1, 2014
• Last Updated: May 10, 2016

Record last verified: 2016-05

Locations

IT (5)