Vorinostat in Combination With Bortezomib, Doxorubicin and Dexamethasone (VBDD) in Patients With Refractory or Relapsed Multiple Myeloma (MM)

NCT ID: NCT01394354

Last Updated: 2016-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2015-12-31

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.

Conditions

Multiple Myeloma in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Vorinostat. To determine the MTD, dose escalation for Vorinostat will be conducted following the "3 + 3 design The first cohort of 3 patients will be given 100mg/d on days 1-4, 8-11, 15-18. The second cohort of 3 new patients will be treated with Vorinostat 200mg/d. The third cohort will be given Vorinostat 300mg/d. Cycles will be repeated every 28 days. Maximum treatment cycles: 6. Bortezomib will be administered intravenously (i.v.) 1.3mg/m2 BSA an days 1, 8, 15.

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

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

Group Type: EXPERIMENTAL

Vorinostat

Intervention Type: DRUG

Vorinostat 100 mg/d p.o., on day 1-4, 8-11, and 15-18 /28 day treatment cycle 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 p.o. and the third cohort will be given Vorinostat with 300 mg/d p.o.

Bortezomib

Intervention Type: DRUG

1.3mg/m2 (days 1,8,15)/28 day treatment cycle, i.v., for max. 6 treatment cycles

Doxorubicin

Intervention Type: DRUG

18mg/m2 i.v. (days 1 and 8)/ 28 day treatment cycle, max. 6 treatment cycles

Dexamethasone

Intervention Type: DRUG

40mg abs. p.o. (days 1,8,15,22) 1st treatment cycle, 20mg abs. p.o.(days 1,8,15,22) 2-6 treatment cycles

Interventions

Vorinostat

Vorinostat 100 mg/d p.o., on day 1-4, 8-11, and 15-18 /28 day treatment cycle 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 p.o. and the third cohort will be given Vorinostat with 300 mg/d p.o.

Intervention Type: DRUG

Bortezomib

1.3mg/m2 (days 1,8,15)/28 day treatment cycle, i.v., for max. 6 treatment cycles

Intervention Type: DRUG

Doxorubicin

18mg/m2 i.v. (days 1 and 8)/ 28 day treatment cycle, max. 6 treatment cycles

Intervention Type: DRUG

Dexamethasone

40mg abs. p.o. (days 1,8,15,22) 1st treatment cycle, 20mg abs. p.o.(days 1,8,15,22) 2-6 treatment cycles

Intervention Type: DRUG

Other Intervention Names

ZOLINZA®, ATC code: L01XX; VELCADE®, ATC code: L01XX32; ADRIMEDAC®; FORTECORTIN®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

University Hospital Freiburg

OTHER

Sponsor Role: lead

Responsible Party

Monika Engelhardt

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Monika Engelhardt, MD

Role: PRINCIPAL_INVESTIGATOR

University of Freiburg Medical School

Locations

University Medical Center Freiburg

Freiburg im Breisgau, , Germany

Countries

Germany

Other Identifiers

00658, MK-0683-201

Identifier Type: -

Identifier Source: org_study_id