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

NCT01394354 | Completed Phase 1

• 1 other identifier: 00658, MK-0683-201
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma in Relapse

Keywords

Multiple Myeloma relapsed refractory

Outcome Measures

Primary Outcomes (1)

• Maximal Tolerated Dose (MTD)

  The Maximal Tolerated Dose (MTD) is estimated as the highest dose at which less than two DLTs in 6 patients are observed in the first cycle. MTD estimation is based on the phase I part of the trial. However, the number of DLT's in the first cycle of the phase II patients will be inspected and discussed as well. The primary target variable is the occurrence of any dose-limiting toxicity (DLT) in MM patients during the first 28 days of treatment.

  28 days (within first treatment cycle)

Secondary Outcomes (6)

• Response

  up to 1 year after inclusion of the last patient

• Rates of Adverse Events (AE),Serious Adverse Events and AEs leading to permanent treatment discontinuation

  9 months

• Quality of Life

  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)

• Duration of Response

  up to one year after inclusion of the last patient

• Progression-free survival (PFS)

  up to 1 year after inclusion of the last patient

Study Arms (1)

1

EXPERIMENTAL

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.

Drug: Vorinostat; Drug: Bortezomib; Drug: Doxorubicin; Drug: Dexamethasone

Interventions

Vorinostat 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.

Also known as: ZOLINZA®, ATC code: L01XX

1

Bortezomib DRUG

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

Also known as: VELCADE®, ATC code: L01XX32

1

Doxorubicin DRUG

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

Also known as: ADRIMEDAC®

1

Dexamethasone 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

Also known as: FORTECORTIN®

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Freiburg: lead
• Merck Sharp & Dohme LLC: collaborator
• Janssen-Cilag Ltd.: collaborator

Study Sites (1)

University Medical Center Freiburg

Freiburg im Breisgau, 79106, Germany

Location

MeSH Terms

Interventions

Vorinostat; Bortezomib; Doxorubicin; Dexamethasone; dexamethasone acetate

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Monika Engelhardt, MD

  University of Freiburg Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: June 21, 2011
• First Posted: July 14, 2011
• Study Start: August 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 6, 2016

Record last verified: 2016-04

Locations

DE (1)