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

Browse trials for

• Multiple Myeloma 3,632
• Neoplasms, Plasma Cell 2,306

Keywords

• Multiple Myeloma relapsed refractory

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 34 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Lead sponsor

University Hospital Freiburg is the lead sponsor of 91 studies on the registry; 18 are open to participants now.

Study arms

• Experimental
  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.

  Drug: Vorinostat · Drug: Bortezomib · Drug: Doxorubicin · Drug: Dexamethasone

Interventions

• DrugVorinostat

  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

• DrugBortezomib

  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

• DrugDoxorubicin

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

  Also known as: ADRIMEDAC®

• DrugDexamethasone

  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®

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.

   Time frame: 28 days (within first treatment cycle)

Secondary outcomes

1. Response

   complete remission (CR, including stringent CR \[sCR\]), very good partial response (vgPR), partial remission (PR), stable disease (SD), progressive disease (PD). These parameters will be evaluated according to IMWG criteria.

   Time frame: up to 1 year after inclusion of the last patient

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

   throughout time of treatment (6 months) + 3 months after end of treatment (Follow-up). Rates of AE, Serious AE and AEs leading to permanent treatment discontinuation will be provided with accompanying 2-sided 95% confidence intervals. Safety parameters will be analyzed descriptively. An AE is any untoward medical occurrence in a patient administered any dose of VBDD study drugs and is defined in detail in the clinical trial protocol. An AE can be any unfavorable sign (incl. an abnormal lab and ECG-findings etc.), symptom, or disease related or not to the study drug.

   Time frame: 9 months

3. Quality of Life

   Assessment with Quality of Life-Questionnaire SF-12

   Time frame: 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)

4. Duration of Response

   Clinical assessment

   Time frame: up to one year after inclusion of the last patient

5. Progression-free survival (PFS)

   estimation by using Kaplan-Meier method

   Time frame: up to 1 year after inclusion of the last patient

6. Overall survival (OS)

   estimation by using Kaplan-Meier method

   Time frame: up to 1 year after inclusion of the last patient