Nelfinavir and Lenalidomide/Dexamethasone in Progressive Multiple Myeloma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01555281|
Recruitment Status : Active, not recruiting
First Posted : March 15, 2012
Last Update Posted : January 7, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Nelfinavir Drug: Lenalidomide Drug: Dexamethasone||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nelfinavir and Lenalidomide/Dexamethasone in Patients With Progressive Multiple Myeloma That Have Failed Lenalidomide-containing Therapy - A Single Arm Phase I/II Trial|
|Actual Study Start Date :||February 23, 2012|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Nelfinavir and Lenalidomide/Dexamethasone
Phase I: Cycles 1-4 (1 cycle = 28 days) Lenalidomide: 25 mg per day p.o., day 1 to 21 Dexamethasone: 40/20 mg per day p.o., days 1, 8, 15, 22 Nelfinavir: Dose escalation in cohorts of 3 patients
Phase II: Cycles 1-4 (1 cycle = 28 days) Lenalidomide: 25 mg per day p.o., day 1 to 21 Dexamethasone: 40/20 mg per day p.o., days 1, 8, 15, 22 Nelfinavir: Dose established in phase I twice daily p.o., day 1 to 21
In phase II, the recommended dose of nelfinavir will be administered orally twice daily (in the morning and in the evening) on d1-d21 every 28 days for a maximum of 4 cycles
Other Name: Viracept
25 mg of lenalidomide (capsules) will be administered orally daily on d1-d21 every 28 days for a maximum of 4 cycles
Other Name: Revlimid
40 mg (for patients <75 years) or 20 mg (for patients ≥75 years) of dexamethasone (tablets) will be administered orally once per day on d1, 8, 15 and 22 every 28 days for a maximum of 4 cycles
- Phase I: Dose limiting toxicity [ Time Frame: Until up to 4 weeks after start of trial therapy ]
- Phase II: Overall response [ Time Frame: 16 weeks after the start of trial therapy ]
- Phase I/II: Frequency and percent of occurrence of adverse events during each cycle of treatment, and within patients [ Time Frame: Until 30 days after up to 16 weeks of trial therapy ]
- Phase I/II: Disease control, i.e. no progression at 16 weeks after start of trial therapy [ Time Frame: At 16 weeks after the start of trial therapy ]
- Phase I/II: Duration of response [ Time Frame: Duration from first observation of response to the time of disease progression, with deaths due to causes other than progression censored, assessed until an expected maximum of 3 years ]
- Phase I/II: Overall survival [ Time Frame: At 6 months after start of trial therapy ]
- Phase I/II: Progression free survival [ Time Frame: Progression free survial time ]
- Phase I/II: Time to progression [ Time Frame: Duration from start of treatment to disease progression, with deaths due to causes other than progression censored, assessed until an expected maximum of 3 years ]
- Phase I: Overall response [ Time Frame: 16 weeks after the start of trial therapy ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01555281
|Istituto Europeo di Oncologia IEO|
|Milano, Italy, 20141|
|University of Torino|
|Torino, Italy, 10127|
|Aarau, Switzerland, 5001|
|Baden, Switzerland, 5404|
|Istituto Oncologico Svizzera Italiana IOSI|
|Bellinzona, Switzerland, 6500|
|Bern, Switzerland, 3010|
|Chur, Switzerland, 7000|
|Olten, Switzerland, 4600|
|Kantonsspital St. Gallen|
|St. Gallen, Switzerland, 9007|
|Thun, Switzerland, 3600|
|Zürich, Switzerland, 8091|
|Study Chair:||Felicitas Hitz, MD||Kantonsspital, CH-9007 St. Gallen|