Multiple Myeloma Clinical Trial
Official title:
A National, Multi-Center, Open-Label Study of Velcade in Combination With Melphalan and Prednisone (V-MP) in Older Untreated Multiple Myeloma Patients.
Verified date | January 2011 |
Source | PETHEMA Foundation |
Contact | n/a |
Is FDA regulated | No |
Health authority | Spain: Ministry of Health |
Study type | Interventional |
This protocol is planned as a multicentric, national, open-label trial designed to evaluate, first, optimal dose of Velcade® (Bortezomib) in combination with melphalan and prednisone. After optimal dose is known, the second aim is evaluate safety and tolerance of V-MP plan, in respond terms, in a cohort of 60 patients. Finally, the entire results will be compared with those obtained from a series of 100 patients, all of them over 70 years old, diagnosed of Multiple Myeloma belonging to the GEM protocol finished in May 2003
Status | Completed |
Enrollment | 60 |
Est. completion date | December 2008 |
Est. primary completion date | January 2007 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 65 Years and older |
Eligibility |
Inclusion Criteria: - 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. - Age over 65 years. - Patient recently diagnosed with symptomatic Multiple Myeloma based on standard criteria and that has not received any previous chemotherapy treatment for Multiple Myeloma. - Patient has measurable disease, defined as follows: For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of = 200 mg/24 hours. For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan). In patients with oligo-secretory multiple myeloma, the serum and/or urine M-protein measurements are very low and difficult to follow for response assessment. In patients with non-secretory multiple myeloma, there is no M-protein in serum or urine. - Patient has a Karnofsky performance status higher 60%. - Patient has a life-expectancy >3 months. - Patient has the following laboratory values within 14 days before Baseline visit (Day 1 of Cycle 1, before study drug administration: Platelet count = 100x109/L, hemoglobin = 8 g/dl and absolute neutrophil count (ANC) = 1.0x109/L. Corrected serum calcium < 14mg/dl. Aspartate transaminase (AST): = 2.5 x the upper limit of normal. Alanine transaminase (ALT): ): = 2.5 x the upper limit of normal. Total bilirubin: =1.5 x the upper limit of normal. Serum creatinine value = 2mg/dl. Exclusion Criteria: - Patient previously received treatment with Velcade. - Patient previously received treatment for Multiple Myeloma. - Patient had major surgery within 4 weeks before enrollment. - Patient has a platelet count < 100 x 109/L within 14 days before enrollment. - Patient has an absolute neutrophil count < 1.0 x 109/L within 14 days before. - Patient has < Grade 2 peripheral neuropathy within 14 days before enrollment. - Patient has hypersensitivity to bortezomib, boron or mannitol. - Patient has received other investigational drugs within 14 days before enrollment. - Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection. - 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. Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Spain | Hospital Clínic | Barcelona | |
Spain | Hospital de la Santa Creu i Sant Pau | Barcelona | |
Spain | Hospital Germans Trias i Pujol | Barcelona | |
Spain | Hospital Virgen Blanca de León | Leon | |
Spain | Hospital Clínico San Carlos de Madrid | Madrid | |
Spain | Hospital Doce de Octubre | Madrid | |
Spain | Hospital Ramón y Cajal | Madrid | |
Spain | Hospital Universitario de la Princesa | Madrid | |
Spain | Hospital Morales Messeguer | Murcia | |
Spain | Hospital Central de Asturias | Oviedo | Asturias |
Spain | Hospital Son Llatzer | Palma de Mallorca | Mallorca |
Spain | Clínica Universitaria de Navarra | Pamplona | Navarra |
Spain | Hospital Clínico Universitario de Salamanca | Salamanca | |
Spain | Hospital General de Segovia | Segovia | |
Spain | Hospital Universitario de Canarias | Tenerife | Islas Canarias |
Spain | Hospital Clínic | Valencia | |
Spain | Hospital La Fe | Valencia | |
Spain | Hospital Universitario Dr. Peset | Valencia | |
Spain | Hospital Clínico Lozano Blesa | Zaragoza |
Lead Sponsor | Collaborator |
---|---|
PETHEMA Foundation | Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Millennium Pharmaceuticals, Inc. |
Spain,
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
26. McConkey DJ, Pettaway C, Elliott P, et al. The proteasome as a new drug target in metastatic prostate cancer. ATMDACC 7th Annual Genitourinary Oncology Conference, 1998
28. Millenium Pharmaceuticals, Inc. (PS-341) Investigator's Brochure, Version 5.0, 2001
Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, Maas J, Pien CS, Prakash S, Elliott PJ. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res. 1999 Jun 1;59(11):2615-22. — View Citation
Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. — View Citation
Alexanian R, Dimopoulos M. The treatment of multiple myeloma. N Engl J Med. 1994 Feb 17;330(7):484-9. Review. — View Citation
Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B. Primary dexamethasone treatment of multiple myeloma. Blood. 1992 Aug 15;80(4):887-90. — View Citation
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996 Jul 11;335(2):91-7. — View Citation
Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest. 2001 Feb;107(3):241-6. Review. — View Citation
Bataille R, Harousseau JL. Multiple myeloma. N Engl J Med. 1997 Jun 5;336(23):1657-64. Review. — View Citation
Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996 Nov 1;274(5288):782-4. — View Citation
Bladé J, Samson D, Reece D, Apperley J, Björkstrand 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. — View Citation
Case DC Jr, Lee DJ 3rd, Clarkson BD. Improved survival times in multiple myeloma treated with melphalan, prednisone, cyclophosphamide, vincristine and BCNU: M-2 protocol. Am J Med. 1977 Dec;63(6):897-903. — View Citation
Driscoll J. The role of the proteasome in cellular protein degradation. Histol Histopathol. 1994 Jan;9(1):197-202. Review. — View Citation
Goldberg AL, Stein R, Adams J. New insights into proteasome function: from archaebacteria to drug development. Chem Biol. 1995 Aug;2(8):503-8. Review. — View Citation
Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. — View Citation
Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma: an overview of published trials. J Clin Oncol. 1992 Feb;10(2):334-42. — View Citation
Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J, Anderson KC. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001 Apr 1;61(7):3071-6. — View Citation
Huang YW, Hamilton A, Arnuk OJ, Chaftari P, Chemaly R. Current drug therapy for multiple myeloma. Drugs. 1999 Apr;57(4):485-506. Review. — View Citation
Koepp DM, Harper JW, Elledge SJ. How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell. 1999 May 14;97(4):431-4. Review. — View Citation
Mileshkin L, Biagi JJ, Mitchell P, Underhill C, Grigg A, Bell R, McKendrick J, Briggs P, Seymour JF, Lillie K, Smith JG, Zeldis JB, Prince HM. Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age. Blood. 2003 Jul 1;102(1):69-77. Epub 2003 Mar 13. — View Citation
Oken MM. Management of Myeloma: Current and Future Approaches. Cancer Control. 1998 May;5(3):218-225. — View Citation
Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell. 1994 Sep 9;78(5):773-85. — View Citation
Raje N, Anderson K. Thalidomide--a revival story. N Engl J Med. 1999 Nov 18;341(21):1606-9. — View Citation
Read MA, Neish AS, Luscinskas FW, Palombella VJ, Maniatis T, Collins T. The proteasome pathway is required for cytokine-induced endothelial-leukocyte adhesion molecule expression. Immunity. 1995 May;2(5):493-506. — View Citation
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. — View Citation
Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood. 2006 Nov 15;108(10):3458-64. Epub 2006 Jul 13. — View Citation
Richter-Ruoff B, Wolf DH. Proteasome and cell cycle. Evidence for a regulatory role of the protease on mitotic cyclins in yeast. FEBS Lett. 1993 Dec 20;336(1):34-6. — View Citation
Sherr CJ. Cancer cell cycles. Science. 1996 Dec 6;274(5293):1672-7. Review. — View Citation
Smith ML, Newland AC. Treatment of myeloma. QJM. 1999 Jan;92(1):11-4. Review. — View Citation
Westin J. Conventional chemotherapy in multiple myeloma. Pathol Biol (Paris). 1999 Feb;47(2):169-71. — View Citation
Zetter BR. Adhesion molecules in tumor metastasis. Semin Cancer Biol. 1993 Aug;4(4):219-29. Review. — View Citation
* Note: There are 32 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Determinate the efficacy of combination velcade, melphalan, prednisone | 1 year | No | |
Secondary | Assess safety and tolerability | 1 year | Yes | |
Secondary | Assess potential superiority of this regimen versus historical controls with melphalan and prednisone alone | 2 years | No | |
Secondary | Evaluate efficacy in terms of progression-free survival and overall survival | 5 years | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05027594 -
Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02412878 -
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
|
Phase 3 | |
Completed |
NCT01947140 -
Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Recruiting |
NCT05971056 -
Providing Cancer Care Closer to Home for Patients With Multiple Myeloma
|
N/A | |
Recruiting |
NCT05243797 -
Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation
|
Phase 3 | |
Active, not recruiting |
NCT04555551 -
MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05618041 -
The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies
|
N/A | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Recruiting |
NCT03412877 -
Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer
|
Phase 2 | |
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Recruiting |
NCT03570983 -
A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion
|
Phase 2 | |
Completed |
NCT03665155 -
First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody
|
Phase 1/Phase 2 | |
Terminated |
NCT03399448 -
NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells)
|
Phase 1 | |
Completed |
NCT02812706 -
Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT05024045 -
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
|
Phase 1 | |
Active, not recruiting |
NCT03989414 -
A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM)
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03792763 -
Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients
|
Phase 2 | |
Withdrawn |
NCT03608501 -
A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation
|
Phase 2 | |
Recruiting |
NCT04537442 -
Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02546167 -
CART-BCMA Cells for Multiple Myeloma
|
Phase 1 |