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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. Identifier: NCT01555281
Recruitment Status : Active, not recruiting
First Posted : March 15, 2012
Last Update Posted : January 13, 2021
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Nelfinavir Drug: Lenalidomide Drug: Dexamethasone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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

Drug: Nelfinavir
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

Drug: Lenalidomide
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

Drug: Dexamethasone
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

Primary Outcome Measures :
  1. Phase I: Dose limiting toxicity [ Time Frame: Until up to 4 weeks after start of trial therapy ]
  2. Phase II: Overall response [ Time Frame: 16 weeks after the start of trial therapy ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Phase I/II: Overall survival [ Time Frame: At 6 months after start of trial therapy ]
  5. Phase I/II: Progression free survival [ Time Frame: Progression free survial time ]
  6. 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 ]
  7. Phase I: Overall response [ Time Frame: 16 weeks after the start of trial therapy ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient must have given written informed consent (including the drug-specific informed consent for Revlimid) before registration.
  • Multiple myeloma having progressed after at least two months of lenalidomide-containing therapy (progressive disease during treatment with lenalidomide or <60 days after such treatment).
  • Measurable disease for myeloma defined as one of the following:

    1. Serum monoclonal protein (M-protein) ≥10 g/L IgG or ≥5 g/L IgA, IgM, IgD
    2. Urine M-protein ≥200 mg/24h
    3. To be considered only if patient has no evidence of measurable disease with one of the criteria above: serum free light chain (FLC) ratio of kappa/lambda either >1.65 or <0.26 (baseline level of involved FLC has to be ≥100 mg/L)
  • Adverse events from previous treatment has recovered to grade ≤2.
  • Age ≥18 years.
  • WHO performance status 0-2.
  • Adequate hematological values: neutrophils ≥1 x 109/L, platelets ≥75 x 109/L
  • Adequate hepatic function: bilirubin ≤1.5 x ULN, AST and AP ≤2.5 x ULN
  • Adequate renal function: calculated creatinine clearance >50 mL/min, according to the formula of Cockcroft-Gault
  • Adequate cardiac function: EF ≥40% assessed by echocardiography or MUGA scan
  • Negative HIV test.
  • Women are not breastfeeding. Women of child-bearing potential are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. A negative serum pregnancy test (minimum sensitivity of 25 mIU/ml) before inclusion (within 7 days) into the trial is required for all women of child-bearing potential. Men agree not to father a child during participation in the trial and during 12 months thereafter.
  • Patient compliance and geographic proximity allow proper staging and follow-up.

Exclusion Criteria:

  • Previous malignancy within 2 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
  • Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling patient diary, or interfering with compliance for oral drug intake.
  • Concurrent treatment with other experimental drugs or other anti-cancer therapy (chemotherapeutical/biological agents, radiation therapy). Treatment in a clinical trial within 30 days prior to trial entry.
  • Known hypersensitivity or uncontrolled side effects related to trial drug(s) or hypersensitivity to any other component of the trial drugs.
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information.
  • Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes).
  • Unstable cardiovascular disease.
  • Known or clinically suspected myeloma manifestations in the central nervous system.
  • Previous grade 4 adverse events attributable to treatment with lenalidomide.
  • Patients who are on strong CYP3A4 modulators that cannot be replaced at least one week before the first dose of trial drugs and for the period of the trial.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01555281

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Istituto Europeo di Oncologia IEO
Milano, Italy, 20141
University of Torino
Torino, Italy, 10127
Kantonsspital Aarau
Aarau, Switzerland, 5001
Kantonsspital Baden
Baden, Switzerland, 5404
Istituto Oncologico Svizzera Italiana IOSI
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, 3010
Kantonsspital Graubünden
Chur, Switzerland, 7000
Kantonsspital Olten
Olten, Switzerland, 4600
Kantonsspital St. Gallen
St. Gallen, Switzerland, 9007
Thun, Switzerland, 3600
UniversitätsSpital Zürich
Zürich, Switzerland, 8091
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
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Study Chair: Felicitas Hitz, MD Kantonsspital, CH-9007 St. Gallen
Additional Information:
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Responsible Party: Swiss Group for Clinical Cancer Research Identifier: NCT01555281    
Other Study ID Numbers: SAKK 39/10
2010-022035-11 ( EudraCT Number )
000001246 ( Other Identifier: SNCTP )
First Posted: March 15, 2012    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Swiss Group for Clinical Cancer Research:
Multiple Myeloma
Kahler Disease
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors