DoxilÂ® + Melphalan + Velcade (DMV) in Relapsed/Refractory Multiple Myeloma

Status:	Archived
Conditions:	Blood Cancer, Hematology
Therapuetic Areas:	Hematology, Oncology
Healthy:	No
Age Range:	Any
Updated:	7/1/2011
Start Date:	June 2004
End Date:	March 2010

Phase I/II Study of Liposomal Doxorubicin (DoxilÂ®)/Melphalan/Bortezomib (VelcadeÂ®) in Relapsed/Refractory Multiple Myeloma

The median overall survival (OS) of relapsed/refractory multiple myeloma (MM) is less than
nine months. However, phase II data with the proteasome inhibitor bortezomib (VelcadeÂ®) has
been heartening, with 35% overall response rates and median survival of 16 months. In-vitro
data has shown that this agent dramatically increases the sensitivity to chemotherapeutic
agents. Liposomal doxorubicin (Doxil), melphalan, and bortezomib all have different
mechanisms of action and toxicity profiles. Clinical studies employing two drug combinations
with these agents in patients with refractory MM have found favorable efficacy (nearly no
progression of disease) and tolerance data. Thus, the investigators are initiating a phase
I/II study to examine the safety and efficacy of combining all three agents into the regimen
DMV (DoxilÂ® + melphalan + Velcade).

Dose Level 1: Doxil 10 mg/m2, Melphalan 5 mg/m2, Velcade 0.7 mg/m2

Dose Level 2: Doxil 10 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2

Dose Level 3: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2

Dose Level 4: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 1.0 mg/m2

Adjunctive therapy with a bisphosphonate, either pamidronate or zolendronic acid, will be
given monthly.

Dose Escalation Schedule: Dose escalation will occur only after patients have completed at
least two cycles at a given dose level.

1. If 0/3 experience DLT (as defined in attachment Section 6.0), the next three patients
will be escalated by one dose level.

2. If 1/3 experience DLT, 3 additional patients enrolled at this dose level.

- If 0, 1, or 2 of these additional patients experience DLT (i.e. total 3/6), the
dose will be escalated.

- If 3/3 experience DLT (i.e. total 4/6) then the next lower dose will be considered
the MTD..

3. If 2/3 experience DLT, 3 additional patients enrolled at this dose level.

- If 0 or 1 of these additional patients experience DLT (i.e. total 3/6), the dose
will be escalated.

- If 2 or more/3 experience DLT (i.e. total more than 3/6) then the next lower dose
level is MTD

We found this trial at

sites

University of California at San Francisco (UCSF)

500 Parnassus Ave
San Francisco, California 94143

(415) 476-9000