dtZ: Higher Frequency Zoledronic Acid in the Treatment of Multiple Myeloma

Sponsor

Gleneagles Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00263484

Collaborator

Singapore General Hospital (Other), National Cancer Centre, Singapore (Other), Tan Tock Seng Hospital (Other), Seoul National University Hospital (Other), Asan Medical Center (Other), Samsung Medical Center (Other), Chonnam National University Hospital (Other), Christian Medical College, Vellore, India (Other), Tata Memorial Hospital (Other)

Enrollment

Locations

Arm

Duration (Months)

5.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: dexamethasone Drug: thalidomide Drug: zoledronic acid	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2005

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: "dtZ" regimen, Initial therapy To test the efficacy of the "dtZ" regimen in previously untreated patients with multiple myeloma.	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. Other Names: DEXAMETHASONE BEACONS Drug: thalidomide 100 mg, PO (orally) on days 1-21 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops. Other Names: THALOMID (PHARMION) THADO (TTY) Drug: zoledronic acid 4 mg, IV (in the vein) on day 1 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops. Other Names: ZOMETA

Arm

Intervention/Treatment

Experimental: "dtZ" regimen, Initial therapy

To test the efficacy of the "dtZ" regimen in previously untreated patients with multiple myeloma.

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.

Other Names:

DEXAMETHASONE BEACONS

Drug: thalidomide

100 mg, PO (orally) on days 1-21 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.

Other Names:

THALOMID (PHARMION)

THADO (TTY)

Drug: zoledronic acid

4 mg, IV (in the vein) on day 1 of each 21 day cycle. 6 Cycles: until progression or unacceptable toxicity develops.

Other Names:

ZOMETA

Outcome Measures

Primary Outcome Measures

1. To determine response rates (RR) and disease progression rates in all MM patients treated with dtZ regimen. [4 months]

Secondary Outcome Measures

To assess overall survival (OS) in all patients treated with dtZ regimen. [4 months]
Assessment of incidence of skeletal related events (SREs). [4 months]
Assessment of percent change in renal function in all patients. [4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Christian Medical College	Vellore	Tamil Nadu	India	632004
2	Tata Memorial Hospital	Mumbai		India	400 012
3	Chonnam National University Hwasun Hospital	Kwangju		Korea, Republic of	519-809
4	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
5	Samsung Medical Center, Seoul, South Korea	Seoul		Korea, Republic of	135-710
6	ASAN Medical Center, University of Ulsan, South Korea	Seoul		Korea, Republic of	138-736
7	Singapore General Hospital	Singapore		Singapore	169608
8	National Cancer Centre, Singapore	Singapore		Singapore	169610
9	Gleneagles Hospital, Singapore	Singapore		Singapore	258500
10	Tan Tock Seng Hospital, Singapore	Singapore		Singapore	308433