Nelfinavir and Lenalidomide/Dexamethasone in Progressive Multiple Myeloma
Status:
Active, not recruiting
Trial end date:
2021-12-01
Target enrollment:
Participant gender:
Summary
There is a great need for treatment options in patients with multiple myeloma (MM) after
failure of the lenalidomide/dexamethasone regimen as there is no established standard active
therapy for these patients.
Combining nelfinavir, a drug targeting both the proteasome and PI3K/Akt pathway, with
lenalidomide, may restore lenalidomide-sensitivity to the disease as has been shown in vivo
for the PI3K/Akt inhibitor perifosine and the proteasome inhibitor bortezomib.
Patients expected to be included in the trial are heavily pretreated and might not be
candidates for further intensive therapies. The combination of nelfinavir with
lenalidomide/dexamethasone offers also to these patients an alternative. Preliminary
experiences in another SAKK trial with the combination of bortezomib and nelfinavir are
positive with few side effects with nelfinavir doses of up to 1875 mg twice daily (bid). For
the phase I part of the trial a starting dose of 1250 mg nelfinavir bid was chosen, since the
necessary plasma concentration of nelfinavir will not be reached with lower doses.
In case of progression during or after the trial treatment any other lenalidomide- or
bortezomib-based chemotherapy combination could be an option for the patient. However, the
addition of a chemotherapeutic drug like cyclophosphamide or doxorubicin has known side
effects like hematological toxicities, nausea, vomiting and hair loss.
The aim of this trial is to demonstrate that the combination of nelfinavir with
lenalidomide/dexamethasone is safe (phase I, dose escalation of nelfinavir) and active (phase
II). Patients who do not respond to trial medication will stop trial treatment after 4 months
of therapy at the latest.
If the combination of nelfinavir with lenalidomide/dexamethasone should prove to be safe and
efficient in treatment of lenalidomide-refractory MM, this would be the first orally
available treatment for these patients and establish a new class of drugs (human
immunodeficiency virus (HIV) protease inhibitors) as active antineoplastic agents in MM. In
addition this would establish the concept of "re-sensitizing" patients to lenalidomide
therapy and demonstrate the effect of nelfinavir on proteasomal degradation and Akt
phosphorylation in cancer patients in vivo.