Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

NCT00474929 | Completed Phase 1 Results DMC

• 2 other identifiers: LS068907-000710
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Sorafenib and everolimus may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib and everolimus and to see how well they work in treating patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.

Conditions

Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm

Keywords

recurrent adult Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; stage III multiple myeloma; refractory multiple myeloma; Waldenström macroglobulinemia; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; cutaneous B-cell non-Hodgkin lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent adult grade III lymphomatoid granulomatosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants Reporting a Dose Limiting Toxicity (DLT)

  The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). Dose-limiting toxicity (DLT) is defined as an adverse event attributed (definitely, probably, or possibly) in first cycle to the study treatment and meeting the following criteria: * Grade 4 infection * Grade 4 ANC or PLT * Grade 3 or higher non-hematologic adverse event. NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0 will be used to assess adverse events. For this endpoint, the number of patients reporting a DLT event are tabulated.

  First cycle (28 days) of study treatment

• Proportion of Confirmed Tumor Responses

  A confirmed response is defined to be a CR or PR noted as the objective status for eligible patients during cycles 1-12. Complete Response (CR): * Multiple Myeloma (MM): Negative immunofixation of serum and urine, disappearance of soft tissue plasmacytomas, and normalization of free light chain (FLC) ratio. * Lymphoma: Disappearance of all clinical and radiographic evidence of disease, all lymph nodes of normal size (1.5 cm or less), no splenomegaly. Partial Response (PR): * MM: 50% reduction of serum or urine M-protein or to less than 200mg/day, a 50% reduction in the difference between involved and uninvolved FLC, and 50% reduction in the size of soft tissue plasmacytoma. * Lymphoma: 50% or greater reduction in sum of the products of the dimension for nodal masses; no increase in liver, spleen or node size; no new sites of disease; and a 50% decrease in lymphocyte count if followed at baseline.

  Up to 12 cycles of treatment

Secondary Outcomes (2)

• Survival Time

  Up to 3 years from registration

• Progression Free Survival

  Up to 3 years from registration

Study Arms (2)

Multiple Myeloma

EXPERIMENTAL

Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day; Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day; Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day; Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day; Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;

Drug: RAD001; Drug: Sorafenib

Lymphoma

EXPERIMENTAL

Phase I: Dose level 0: Sorafenib 200 mg twice daily, RAD001 5mg every other day; Dose level 1: Sorafenib 200 mg twice daily, RAD001 5mg every day; Dose level 2: Sorafenib 400 mg twice daily, RAD001 5mg every day; Dose level 3: Sorafenib 400 mg twice daily, RAD001 10mg every day; Phase II: Sorafenib 200 mg twice daily, RAD001 5mg every day;

Drug: RAD001; Drug: Sorafenib

Interventions

RAD001 DRUG

Phase I: Dose level 0: RAD001 5mg every other day; Dose level 1: RAD001 5mg every day; Dose level 2: RAD001 5mg every day; Dose level 3: RAD001 10mg every day; Phase II: RAD001 5mg every day;

Also known as: Everolimus

Lymphoma; Multiple Myeloma

Sorafenib DRUG

Phase I: Dose level 0: Sorafenib 200 mg twice daily; Dose level 1: Sorafenib 200 mg twice daily; Dose level 2: Sorafenib 400 mg twice daily; Dose level 3: Sorafenib 400 mg twice daily; Phase II: Sorafenib 200 mg twice daily;

Also known as: sorafenib tosylate

Lymphoma; Multiple Myeloma

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed diagnosis of 1 of the following: * Multiple myeloma * Non-Hodgkin's lymphoma * Hodgkin's lymphoma * Relapsed or refractory disease * Measurable disease, as defined according to diagnosis as follows: * Multiple myeloma, meeting 1 of the following criteria: * Serum monoclonal protein ≥ 1.0 g/dL * Urine monoclonal protein ≥ 200 mg by 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% (evaluable disease) * Lymphoma, meeting 1 of the following criteria: * Measurable disease by CT scan or MRI or PET/CT scan, defined as ≥ 1 lesion that has a single diameter of ≥ 2 cm OR tumor cells in the blood ≥ 5 x10\^9/L * Skin lesions can be used if the area is ≥ 2 cm in ≥ 1 diameter and photographed with a ruler * Lymphoplasmacytic lymphoma without measurable lymphadenopathy, meeting both of the following criteria: * Bone marrow lymphoplasmacytosis with \> 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy * Quantitative IgM monoclonal protein \> 1,000 mg/dL * Not a candidate for known standard potentially curative therapy PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * ANC ≥ 1,500/mm³ * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 75,000/mm³ * Bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal * AST ≤ 3 times ULN (5 times ULN if liver involvement) * Creatinine ≤ 2.5 times ULN * INR \< 1.5 or activated PTT \< 1.5 times ULN (no concurrent anticoagulants) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for at least 2 weeks after completion of study treatment * No uncontrolled infection * No NYHA class III-IV congestive heart failure * No unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) * No myocardial infarction within the past 6 months * No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg, despite optimal medical management * No known HIV positivity * No other active malignancy requiring treatment * No inability to swallow * No gastrointestinal (GI) function impairment or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small bowel resection) or preclude use of oral medications * No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months * No pulmonary hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks * No severe or uncontrolled medical conditions or other conditions that would preclude study compliance * No liver disease, such as cirrhosis, chronic hepatitis or chronic persistent hepatitis, or uncontrolled infections * No serious nonhealing wound, ulcer, or bone fracture * No evidence or history of serious bleeding diathesis or coagulopathy, such as hemophilia or von Willebrand's disease * No significant traumatic injury within the past 4 weeks * No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) PRIOR CONCURRENT THERAPY: * More than 3 weeks since prior myelosuppressive chemotherapy or biological therapy and recovered * More than 4 weeks since prior major surgery or open biopsy * Lymph node biopsy within past 4 weeks allowed * Prior everolimus allowed * No concurrent immunosuppressant therapy * Concurrent stable chronic doses of steroids (≤ 20 mg of prednisone per day) for disorders other than lymphoma (i.e., rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, asthma) or for pruritus or fever associated with lymphoma allowed * Concurrent corticosteroids at the lowest possible dose necessary to control symptoms in patients with CNS lymphoma allowed * No concurrent CYP450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort) * No other concurrent immunotherapy, radiotherapy, or chemotherapy * No concurrent chronic oxygen therapy * No concurrent warfarin or heparin * No other concurrent investigational therapy

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

Sponsors & Collaborators

• Mayo Clinic: lead
• University of Iowa: collaborator

Study Sites (2)

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1002, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Hodgkin Disease; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Mycosis Fungoides; Sezary Syndrome

Interventions

Everolimus; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoma, T-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Thomas E. Witzig, M.D.
• Organization: Mayo Clinic

witzig.thomas@mayo.edu

Study Officials

• Thomas E. Witzig, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Shaji K. Kumar, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 16, 2007
• First Posted: May 17, 2007
• Study Start: August 29, 2007
• Primary Completion: November 5, 2011
• Study Completion: August 8, 2019
• Last Updated: August 20, 2019
• Results First Posted: July 7, 2016

Record last verified: 2019-02

Locations

US (2)