Higher Frequency Zoledronic Acid in the Treatment of Multiple Myeloma

Multiple Myeloma Clinical Trial

— dtZ  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00263484
• Other study ID #: SQMM01(dtZ)
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2005
• Last updated: July 19, 2011
• Start date: December 2005
• Est. completion date: October 2010

Study information

• Verified date: July 2011
• Source: Gleneagles Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: October 2010
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• dexamethasone
20 mg, PO (orally) on days 1-4, 8-11 and 15-18 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.
• thalidomide
100 mg, PO (orally) on days 1-21 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.
• zoledronic acid
4 mg, IV (in the vein) on day 1 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
India	Tata Memorial Hospital	Mumbai
India	Christian Medical College	Vellore	Tamil Nadu
Korea, Republic of	Chonnam National University Hwasun Hospital	Kwangju
Korea, Republic of	ASAN Medical Center, University of Ulsan, South Korea	Seoul
Korea, Republic of	Samsung Medical Center, Seoul, South Korea	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Singapore	Gleneagles Hospital, Singapore	Singapore
Singapore	National Cancer Centre, Singapore	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital, Singapore	Singapore

Sponsors (10)

Lead Sponsor	Collaborator
Gleneagles Hospital	Asan Medical Center, Chonnam National University Hospital, Christian Medical College, Vellore, India, National Cancer Centre, Singapore, Samsung Medical Center, Seoul National University Hospital, Singapore General Hospital, Tan Tock Seng Hospital, Tata Memorial Hospital

Countries where clinical trial is conducted

India,  Korea, Republic of,  Singapore, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. To determine response rates (RR) and disease progression rates in all MM patients treated with dtZ regimen.		4 months	No
Secondary	To assess overall survival (OS) in all patients treated with dtZ regimen.		4 months	No
Secondary	Assessment of incidence of skeletal related events (SREs).		4 months	No
Secondary	Assessment of percent change in renal function in all patients.		4 months	Yes