Higher Frequency Zoledronic Acid in the Treatment of Multiple Myeloma

NCT ID: NCT00263484

Last Updated: 2011-07-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-12-31

Study Completion Date

2010-10-31

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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"dtZ" regimen, Initial therapy

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

Group Type EXPERIMENTAL

dexamethasone

Intervention Type DRUG

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

Intervention Type DRUG

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

zoledronic acid

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

thalidomide

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

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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DEXAMETHASONE BEACONS THALOMID (PHARMION) THADO (TTY) ZOMETA

Eligibility Criteria

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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)
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Singapore General Hospital

OTHER

Sponsor Role collaborator

National Cancer Centre, Singapore

OTHER

Sponsor Role collaborator

Tan Tock Seng Hospital

OTHER

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role collaborator

Chonnam National University Hospital

OTHER

Sponsor Role collaborator

Christian Medical College, Vellore, India

OTHER

Sponsor Role collaborator

Tata Memorial Hospital

OTHER_GOV

Sponsor Role collaborator

Gleneagles Hospital

OTHER

Sponsor Role lead

Responsible Party

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Gleneagles Hospital, Singapore

Principal Investigators

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Gerrard Teoh, MD

Role: STUDY_CHAIR

Gleneagles Hospital, Singapore

Locations

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Tata Memorial Hospital

Mumbai, Mumbai, India

Site Status

Christian Medical College

Vellore, Tamil Nadu, India

Site Status

Singapore General Hospital

Singapore, , Singapore

Site Status

National Cancer Centre, Singapore

Singapore, , Singapore

Site Status

Gleneagles Hospital, Singapore

Singapore, , Singapore

Site Status

Tan Tock Seng Hospital, Singapore

Singapore, , Singapore

Site Status

Chonnam National University Hwasun Hospital

Gwangju, Gwangju, South Korea

Site Status

Seoul National University Hospital

Seoul, Seoul, South Korea

Site Status

Samsung Medical Center, Seoul, South Korea

Seoul, Seoul, South Korea

Site Status

ASAN Medical Center, University of Ulsan, South Korea

Seoul, Seoul, South Korea

Site Status

Countries

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India Singapore South Korea

References

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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.

Reference Type BACKGROUND
PMID: 11841428 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14534891 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12409330 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12506164 (View on PubMed)

Related Links

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http://www.cbd.sg

Clinic for Blood Disorders and Research (CBD), Gleneagles Hospital, Singapore

Other Identifiers

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SQMM01(dtZ)

Identifier Type: -

Identifier Source: org_study_id

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