Clinical trial NCT01394354: Vorinostat in Combination With Bortezomib, Doxorubicin and Dexamethasone (VBDD) in Patients With Refractory or Relapsed Multiple Myeloma (MM)
Official title: Safety of Vorinostat in Combination With Bortezomib, Doxorubicin and Dexamethasone (VBDD) in Patients With Refractory or Relapsed Multiple Myeloma, A Phase I/II Study, Short Title: VBDD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma in Relapse
Keywords: Multiple Myeloma relapsed refractory
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Janssen-Cilag Ltd.
First posted: 2011-07-14
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary objective of the study is the determination of the maximum tolerated dose (MTD) of Vorinostat (V), given in combination with fixed doses of Doxorubicin (D), Bortezomib (B) and Dexamethasone (D).

Secondary objectives are:

Assessment of safety and tolerability of VBDD; efficacy data of VBDD.

Detailed description: A first cohort of three patients will be treated at the starting dose level of Vorinostat 100 mg/d, on day 1-4, 8-11, and 15-18 in combination with BDD.

The dose level of Vorinostat will be escalated in each new cohort:

if no dose limiting toxicity (DLT) has been observed in the previous dose level in 3 patient, the second cohort of 3 new patients will be treated with Vorinostat 200 mg/d and the third cohort will be given Vorinostat with 300 mg/d.

Bortezomib will be administered intravenously (i.v.) 1.3mg/m2 d1, 8, 15. Doxorubicin will be administered i.v. with a total dose of 18 mg/m2 per cycle (9 mg/m2, d1 and 8).

Dexamethasone will be administered per os (p.o.) with 40mg (first cycle) and 20mg (all other subsequent cycles) on d1, 8, 15, 22.

Eligibility criteria: Inclusion Criteria:

* Patients with refractory or relapsed MM after at least first-line chemotherapy (CTx) or PBSCT (autologous and allogeneic SCT). All lines of relapse are eligible.
* KPS ≥60%
* Adequate BM function
* Adequate hepatic and renal function (AST and ALT ≤2.5 times ULN, Bilirubin ≤1.5 times ULN, eGFR \>20 ml/min)

Exclusion Criteria:

* Patient has had prior treatment with Vorinostat or HDAC inhibitors
* Patients with severe hepatic impairment or acute diffuse infiltrative pulmonary and pericardial disease
* Patient has preexisting NCI CTC ≥grade 3 neuropathy
* Patient with known CNS MM-involvement and/or MM-related/induced meningitis

Primary outcomes:
measure: Maximal Tolerated Dose (MTD)
timeFrame: 28 days (within first treatment cycle)
Secondary outcomes:
measure: Response
timeFrame: up to 1 year after inclusion of the last patient
measure: Rates of Adverse Events (AE),Serious Adverse Events and AEs leading to permanent treatment discontinuation
timeFrame: 9 months
measure: Quality of Life
timeFrame: during screening period (within 28 days) before start of treatment and at EOT (whether after the completion of the anticipated 6 cycles of chemotherapy or at an earlier time point if patient has to stop treatment because of clinical reasons)
measure: Duration of Response
timeFrame: up to one year after inclusion of the last patient
measure: Progression-free survival (PFS)
timeFrame: up to 1 year after inclusion of the last patient
measure: Overall survival (OS)
timeFrame: up to 1 year after inclusion of the last patient
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
Study officials:
affiliation: University of Freiburg Medical School
name: Monika Engelhardt, MD
role: PRINCIPAL_INVESTIGATOR
References: