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

University Hospital Freiburg

Status and phase: Completed; Phase 2; Phase 1

Conditions: Multiple Myeloma in Relapse

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01394354

00658, MK-0683-201

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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34 participants in 1 patient group

1

Experimental group

Description:

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.

Treatment:

Drug: Doxorubicin

Drug: Dexamethasone

Drug: Bortezomib

Drug: Vorinostat