Clinical trial NCT00263484: Higher Frequency Zoledronic Acid in the Treatment of Multiple Myeloma
Official title: An International, Multicenter, Non-Randomized, Open-Labeled Study to Evaluate the Efficacy of Lower Dose Dexamethasone/Thalidomide and Higher Frequency ZOMETA(TM) in the Treatment of Previously Untreated Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Steroids, Fluorinated
Thalidomide
Bisphosphonates
Lead sponsor: Gleneagles Hospital
Sponsor class: OTHER
Collaborators: name: Singapore General Hospital
name: National Cancer Centre, Singapore
name: Tan Tock Seng Hospital
name: Seoul National University Hospital
name: Asan Medical Center
name: Samsung Medical Center
name: Chonnam National University Hospital
name: Christian Medical College, Vellore, India
name: Tata Memorial Hospital
First posted: 2005-12-08
Enrollment: 56
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether lower than conventional doses of dexamethasone and thalidomide; and a higher dosing frequency of zoledronic acid are effective in the treatment of newly-diagnosed multiple myeloma.

Detailed description: Patients with newly-diagnosed multiple myeloma (MM) may be treated using monthly cycles of dexamethasone plus thalidomide (DT). Unfortunately, the use of conventional doses of DT is associated with significant treatment-related morbidity and mortality, which is comparable to that observed with conventional chemotherapy. Hence, for safety reasons, patients frequently receive lower than conventional doses of DT (i.e. dt), and potentially experience a poorer anti-MM effect. The highly-potent aminobisphosphonate, zoledronic acid (Z), has been shown in pre-clinical mouse models to exhibit an impressive anti-MM effect. It is therefore possible to combined dt with Z (i.e. dtZ) to enhance the efficacy of (lower dose) dt. In addition, the anti-tumor effect of dtZ may potentially be augmented by using Z at a higher (three-weekly) dosing frequency.

Eligibility criteria: Inclusion Criteria:

* Age at or above 21 years
* Clinical diagnosis of MM
* Active MM with measurable disease
* Signed written informed consent
* Signed consent for drug safety program for thalidomide

Exclusion Criteria:

* Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)
* Patients with Indolent MM (IMM), or Smouldering MM (SMM)
* Known hypersensitivity (including severe cutaneous reactions) to d, t or Z
* Fulminant sepsis
* Females in the reproductive age group who refuse contraception
* Pregnancy
* 24 hr urinary creatinine clearance time (CCT) \<30 ml/min
* Previous renal transplantation
* Severe peripheral neuropathy
* Recurrent DVT or PE
* Severe arrhythmias and cardiac conduction disorders
* Liver dysfunction of active viral hepatitis
* Osteonecrosis of the jaws (ONJ)

Primary outcomes:
measure: 1. To determine response rates (RR) and disease progression rates in all MM patients treated with dtZ regimen.
timeFrame: 4 months
Secondary outcomes:
measure: To assess overall survival (OS) in all patients treated with dtZ regimen.
timeFrame: 4 months
measure: Assessment of incidence of skeletal related events (SREs).
timeFrame: 4 months
measure: Assessment of percent change in renal function in all patients.
timeFrame: 4 months
Other outcomes:
Locations:
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Kwangju
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Seoul, South Korea
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center, University of Ulsan, South Korea
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre, Singapore
city: Singapore
country: Singapore
facility: Gleneagles Hospital, Singapore
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital, Singapore
Study officials:
affiliation: Gleneagles Hospital, Singapore
name: Gerrard Teoh, MD
role: STUDY_CHAIR
References:
citation: Yaccoby S, Pearse RN, Johnson CL, Barlogie B, Choi Y, Epstein J. Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. Br J Haematol. 2002 Feb;116(2):278-90. doi: 10.1046/j.1365-2141.2002.03257.x.
citation: Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer. 2003 Oct 15;98(8):1735-44. doi: 10.1002/cncr.11701.
citation: Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002 Nov 1;20(21):4319-23. doi: 10.1200/JCO.2002.02.116.
citation: Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. doi: 10.1200/JCO.2003.03.139.