Sorafenib, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT00687674 | Terminated Phase 1 Results DMC

• 7 other identifiers: CDR0000597065P30CA015083MC078A07-006234NCI-2009-01284RV-MM-PI-0142SR06-933
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sorafenib and lenalidomide may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving sorafenib together with lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib when given together with lenalidomide and dexamethasone and to see how well they work in treating patients with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

refractory multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Grade 3 and 4 Adverse Event (Phase I)

  Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Description of Grades: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death

  up to 3 years

• Number of Participants Who Achieve a Confirmed Response (Partial Response [PR], Very Good PR [VGPR], Complete Response [CR], or Stringent CR [sCR]) (Phase II)

  Response that was confirmed on 2 consecutive evaluations during treatment * CR: Complete disappearance of M-protein from serum \& urine on immunofixation, \<5% plasma cells in bone marrow (BM) * sCR: CR plus normal FLC ratio \& absence of clonal cells in BM * VGPR: \>=90% reduction in serum M-component; Urine M-Component \<100 mg per 24 hours; \<=5% plasma cells in BM * PR: \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels

  Duration on Treatment (up to 3 years)

Secondary Outcomes (7)

• Overall Survival (Phase II)

  From registration to death (up to 3 years)

• Time to Disease Progression (Phase II)

  From registration to progression (up to 3 years)

• Changes in Microvessel Density From Baseline to Post-treatment and Correlation With > Clinical Outcomes (Phase II)

  Pre and Post treatment (up to 3 years)

• Change in Apoptosis Rate From Baseline to Post-treatment and Correlation With > Clinical Outcomes (Phase II)

  Pre and Post treatment (up to 3 years)

• Plasma Cell Gene Expression Profiles and Correlation With > Clinical Outcomes

  Post treatment

Study Arms (1)

Sorafenib + Lenalidomide + Dexamethasone

EXPERIMENTAL

Drug: dexamethasone; Drug: sorafenib tosylate; Drug: Lenalidomide

Interventions

dexamethasone DRUG

20 mg orally Days 1, 8, 15, 22 of 28 day cycle

Sorafenib + Lenalidomide + Dexamethasone

sorafenib tosylate DRUG

Phase I - dose escalating: 200mg once daily dose level -2, 200mg once daily dose level -1, 200mg once daily dose level 0, 200mg twice daily dose level 1, 200mg twice daily dose level 2, 400mg AM \& 200mg PM daily dose level 2a, 400mg twice daily dose level 3 orally days 1-28 every 28 days until progression

Sorafenib + Lenalidomide + Dexamethasone

Lenalidomide DRUG

Phase I - dose escalating: 5mg level -2, 10mg level -1, 15mg level 0, 15mg level 1, 25mg level 2, 25mg level 2a, 25mg level 3 orally days 1-21 every 28 days until progression

Sorafenib + Lenalidomide + Dexamethasone

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of multiple myeloma * Relapsed or refractory disease requiring treatment * Measurable disease, as defined by at least 1 of the following: * Serum monoclonal protein ≥ 1.0 g * More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis * Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Monoclonal bone marrow plasmacytosis ≥ 30% (i.e., evaluable disease) * No known standard therapy that is potentially curative for the patient's disease PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * ANC ≥ 1,000/μL * Platelet count ≥ 75,000/μL * Hemoglobin ≥ 9 g/dL * Direct bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST ≤ 3 times ULN (≤ 5 times ULN if the liver is involved) * Creatinine ≤ 2.5 times ULN * Patients with treated or untreated POEMS (Patient-Oriented Evidence That Matters) allowed, provided they satisfy the criteria for measurable disease * No other prior malignancy within the past year except currently treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or prostate cancer not requiring therapy * No other active malignancy requiring treatment that would interfere with the assessments of response of the myeloma to protocol treatment * INR \< 1.5 OR PT/PTT ≤ 1.5 times ULN * Patients receiving anticoagulation treatment with an agent such as warfarin or heparin are allowed * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 methods of effective contraception for 28 days prior, during, and for 28 days after discontinuation of lenalidomide * Willing to provide research samples according to the test schedule * No uncontrolled infection * No NYHA classification III or IV heart disease * No unstable angina (i.e., anginal symptoms at rest), new-onset angina (i.e., began within the past 3 months), or myocardial infarction within the past 6 months * No uncontrolled hypertension, defined as systolic blood pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg, despite optimal medical management * No thrombotic or embolic events within the past 6 months, including cerebrovascular accidents and transient ischemic attacks * More than 4 weeks since prior pulmonary hemorrhage or other bleeding event \> grade 2 * No serious nonhealing wound or ulcer * More than 4 weeks since prior significant traumatic injury * No known positivity for HIV infection or infectious hepatitis, type A, B, or C * No known hypersensitivity to thalidomide or lenalidomide * No prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs * Able to take aspirin (325 mg) daily as prophylactic anticoagulation PRIOR CONCURRENT THERAPY: * Recovered from prior chemotherapy, regardless of interval since last treatment * Prior lenalidomide therapy allowed * More than 4 weeks since prior experimental therapy * More than 4 weeks since prior major surgery or open biopsy * No concurrent enrollment in any other study involving a pharmacologic agent or investigative therapy (i.e., drug, biologic, immunotherapy approaches, gene therapy) whether for symptom control or therapeutic intent * No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (i.e., phenytoin, carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John wort)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Dexamethasone; Sorafenib; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Shaji Kumar
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

Study Officials

• Shaji K. Kumar, M.D.

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2008
• First Posted: June 2, 2008
• Study Start: August 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: August 20, 2019
• Results First Posted: December 26, 2011

Record last verified: 2018-05

Locations

US (1)