Clinical trial NCT01190787: Subcutaneous Velcade Plus Oral Melphalan and Prednisone or Plus Cycloposphamide and Prednisone or Plus Prednisone
Official title: A Multicenter Phase II Study of Subcutaneous Velcade Plus Oral Melphalan and Prdnisone or Plus Cycloposphamide and Prednisone or Plus Prednisone in Newly Diagnosed Elderly Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Elderly Patients
Diagnosis
Velcade subcutaneous
Prednisone
Melphalan
Cyclophosphamide
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Fondazione EMN Italy Onlus
First posted: 2010-08-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This protocol is a single-arm, three-cohort, phase II multicenter study designed to assess the safety and the efficacy of three all-oral combinations: Velcade with continuous low-dose melphalan and prednisone (VMP) or with continuous low-dose cyclophosphamide and prednisone (VCP) or Velcade with low-dose prednisone could be effective and well tolerated (VP).

Detailed description: This protocol is a single-arm, three-cohort, phase II multicenter study designed to assess the safety and the efficacy of VMP and VCP and VP as up-front treatment in elderly MM patients. The combination of weekly subcutaneous administrations of Velcade with continuous low-dose melphalan and prednisone (VMP) or with continuous low-dose cyclophosphamide and prednisone (VCP) or Velcade with low-dose prednisone could be effective and well tolerated (VP).

Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).

The pre-treatment period includes screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility. The screening period includes the availability of inclusion criteria described above.

The treatment period includes induction and maintenance.

Subjects receive:

1. Induction therapy:

   nine 4-week courses of Velcade/Melphalan/Prednisone (VMP) or nine 4-week courses of Velcade/Cyclophosphamide/Prednisone (VCP) or Nine 4-week courses of Velcade/Prednisone (VP).
2. Maintenance therapy:

Velcade alone During the induction period patients will attend periodic study centre visits each scheduled Velcade administration in order to asses the toxicity and efficacy of the treatment. During the maintenance period, all patients will attend study centre visits every 4 weeks, until development of confirmed PD. The response will be assessed after each cycle.

During the LTFU period, after development of confirmed PD, all patients are to be followed for survival during the LTFU period every 3 months via telephone or office visit.

The duration of treatment period, including the maintenance treatment is approximately 3 years. The duration of LTFU is approximately 2 years, for a total of 5 years. the occurance of PD will determine the duration of progression-free survival of each patient(secondary objective). The occurrence of death will determine the duration of overall survival (secondary objective).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 75 years old or age \< 75 years with abnormal cardiac, pulmonary, renal or hepatic function (unsuitable for protocol with standard inclusion/exclusion 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.
* 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 Velcade therapy.
* 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 therapy.
* Patient was a newly diagnosed multiple myeloma based on standard criteria
* Patient has measurable disease, defined as follows:
* Secretory myeloma: 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;
* Non-secretory myeloma: \> 30% plasma cells in the bone marrow and at least one plasmacytoma \> 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
* Patient has a Karnofsky performance status \> 50%.
* Patient has a life-expectancy \>3 months
* Pretreatment clinical laboratory values within 14 days of enrolment:
* platelet count ≥ 80x109/L
* hemoglobin ≥ 8 g/dL
* absolute neutrophil count (ANC) ≥ 1.0x109/L
* AST ≤ 2.5 times the upper limit of normal
* ALT ≤ 2.5 times the upper limit of normal
* total bilirubin ≤ 1.5 times the upper limit of normal
* cleareance creatinine ≥ 20 ml/min

Exclusion Criteria:

* Any serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from signing the informed consent form or placed the subjects at unacceptable risk.
* Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; \< to the equivalent of dexamethasone 40 mg/day for 4 days).
* Pregnant or lactating females
* Known positive for HIV or active infectious hepatitis type A, B or C
* Peripheral neuropathy or neuropatic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0
* Infiltrative pulmonary disease

Primary outcomes:
measure: Very Good Partial Response, Complete response rate , Partial response rate
timeFrame: 5 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 5 years
measure: Time to progression
timeFrame: 5 years
measure: Time to Next Therapy
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Time to response
timeFrame: 5 years
measure: Duration of response
timeFrame: 5 years
measure: Response rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - SC Ematologia U
Study officials:
affiliation: Fondazione EMN Italy Onlus
name: Mario Boccadoro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.
citation: Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.