Clinical trial NCT00708292: A Phase I-Ib/II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 Alone and in Combination With Bortezomib, With or Without Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma.
Official title: An Open-label, Multi-center, Phase I-Ib/II Study of AUY922 Administered as Single Agent and in Combination With Bortezomib With or Without Dexamethasone in Adult Patients in Relapse or Refractory Multiple Myeloma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: AUY922
Multiple Myeloma
HSP90 inhibitors
Phase I/II
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-07-02
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase I-Ib/II, open-label, multicenter study of AUY922 administered intravenously in patients with multiple myeloma to determine the maximum tolerated dose. The Phase II part will investigate the efficacy of AUY922 in patients with multiple myeloma. Additionally, the study includes a Phase Ib combination part of AUY922 administered in combination with bortezomib, to determine the maximum tolerated dose of the combination drugs in patients with multiple myeloma.


Eligibility criteria: Inclusion criteria:

* Patients must have a diagnosis of active multiple myeloma.
* Phase I and Phase II part: Patients must have received at least 2 but not more than 4 prior line of therapy and their disease has progressed during or after last therapy.
* Phase Ib part: Patients must have received no more than 2 prior lines of therapy (excluding dexamethasone as single agent).
* ECOG Performance Status of ≤ 2.
* Patients must have acceptable neutrophil and platelet counts as well as adequate kidney and liver function.
* Patients must have magnesium levels above lower limit of normal or correctable with supplements.
* Patients must be willing and able to undergo bone marrow biopsy/aspirate.
* Able to sign informed consent.

Exclusion criteria:

* Prior treatment with any HSP90 or HDAC inhibitor for the treatment of multiple myeloma.
* Patients with unresolved diarrhea ≥ CTCAE grade 2.
* Patients with acute or chronic liver disease.
* Patients using medications that have a relative risk of prolonging the QT interval.
* Clinically significant cardiac diseases.
* Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome).
* Pregnant or lactating women.
* Fertile women of childbearing potential (WCBP) not using adequate contraception.
* Male patients whose partners are WCBP, not using adequate contraception.
* Patients who unwilling or unable to comply with the protocol.
* Phase Ib part: Peripheral neuropathy ≥ CTCAE grade 1.
* Phase Ib part: Prior treatment with bortezomib.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: The safe dose of AUY922 when administered once a week.
timeFrame: 54 weeks (Maximum Tolerated Dose (MTD))
Secondary outcomes:
measure: The safe dose of AUY922 when administered once a week in combination with bortezomib and dexamethasone.
timeFrame: 24 weeks (MTD determination of dual and triple combination)
measure: Efficacy of AUY922 administered once a week alone and in combination
timeFrame: at baseline and every 2 cycles (time to document tumor progression)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona Cancer Clinical Research Unit
state: Arizona
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)
state: Texas
city: Melbourne
country: Australia
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Seggewiss-Bernhardt R, Bargou RC, Goh YT, Stewart AK, Spencer A, Alegre A, Blade J, Ottmann OG, Fernandez-Ibarra C, Lu H, Pain S, Akimov M, Iyer SP. Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma. Cancer. 2015 Jul 1;121(13):2185-92. doi: 10.1002/cncr.29339. Epub 2015 Mar 24.