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LymphomaPhase 1/2NCT00474929

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

A Phase 1/2 study testing RAD001 and Sorafenib in people with Lymphoma and Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
RAD001 and Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
2 sitesUnited States
Study dates
29 Aug 2007to 8 Aug 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Holden Comprehensive Cancer Center at University of Iowa

    Iowa City, Iowa, 52242-1002

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I/II Study of the Raf Kinase/VEGFR Inhibitor Sorafenib in Combination With the mTOR Inhibitor RAD001 (Everolimus) in Patients With Relapsed Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Multiple Myeloma

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.

Read the detailed description

OBJECTIVES:

  • Determine the maximum tolerated dose (MTD) of sorafenib tosylate and everolimus in patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.
  • Determine the toxicity of this regimen in these patients.
  • Evaluate the therapeutic activity of this regimen in these patients.
  • Evaluate the pharmacokinetic interaction of this regimen.
  • Correlate clinical (toxicity and/or tumor response or activity) effects with pharmacologic (pharmacokinetic/pharmacodynamic) parameters and/or biologic (correlative laboratory) results.

OUTLINE: This is a multicenter, dose-escalation, phase I study followed by a phase II study.

  • Phase I (closed to accrual as of 2/10/2009): Patients receive oral sorafenib tosylate and oral everolimus on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sorafenib tosylate and everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 out of at most 6 patients experience a Dose Limiting Toxicity (DLT).

  • Phase II: Patients receive oral sorafenib tosylate twice daily and oral everolimus once daily at the MTD determined in phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow are collected periodically during the study and analyzed by flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. Patients enrolled in phase I also undergo blood sample collection on days 8 and 15 during course 1 and on day 1 of each subsequent course for pharmacokinetic studies.

After completion of study treatment, patients are followed every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 103 patients will be accrued for this study.

Being tested
RAD001, Sorafenib
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
Medical subject headings
Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Hodgkin Disease, Lymphoma, T-Cell, Cutaneous, Waldenstrom Macroglobulinemia, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAD001Drug

    Also called Everolimus

    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;

  • SorafenibDrug

    Also called sorafenib tosylate

    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;

Study groups in NCT00474929
Study groupRoleWhat they receive
Multiple MyelomaExperimentalPhase 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;
Receives: Drug: RAD001; Drug: Sorafenib
LymphomaExperimentalPhase 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;
Receives: Drug: RAD001; Drug: Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: First cycle (28 days) of study treatment

  2. 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.

    Measured: Up to 12 cycles of treatment

Secondary outcomes (2)

  1. Survival Time

    Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: Up to 3 years from registration

  2. Progression Free Survival

    Progression Free Survival is defined as the time from registration to the earliest date documentation of disease progression or death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier.

    Measured: Up to 3 years from registration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2007 (estimated)
  2. Study start29 Aug 2007
  3. Primary completion5 Nov 2011
  4. Study completion8 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00474929
Sponsor's protocol ID
LS0689
Other IDs
07-000710, LS0689
Status last verified
Feb 2019
First submitted
16 May 2007
Last updated
20 Aug 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RAD001 and Sorafenib in people with Lymphoma and Multiple Myeloma and Plasma Cell Neoplasm, run by Mayo Clinic at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting a Dose Limiting Toxicity (DLT) (time frame: First cycle (28 days) of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00474929.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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