NCT00671112

Brief Summary

RATIONALE: Everolimus and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with bortezomib in treating patients with relapsed or refractory lymphoma.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 2, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 5, 2008

Completed
27 days until next milestone

Study Start

First participant enrolled

June 1, 2008

Completed
7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed
Last Updated

October 28, 2015

Status Verified

October 1, 2015

Enrollment Period

7.3 years

First QC Date

May 2, 2008

Last Update Submit

October 27, 2015

Conditions

714leukemiaLymphoma

Keywords

recurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaWaldenstrom's macroglobulinemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomarefractory hairy cell leukemiaB-cell chronic lymphocytic leukemiarefractory chronic lymphocytic leukemiahairy cell leukemiacutaneous B and T cell lymphomatransformed lymphomatransformed B and T cell cutaneous lymphomarelapsed or refractory diffuse large B cell lymphomaextranodal T cell lymphomasanaplastic large cell lymphomaangioimmunoblastic T cell lymphomaPTCL-NOSnasal or disseminated extranodal T/NK lymphomaenteropathy-associated T cell lymphomahepatosplenic gamma/delta T cell lymphomasubcutaneous panniculitis-like T cell lymphomaT-prolymphocytic leukemiaadult T-cell leukemia/lymphomalarge granular lymphocytic leukemiaaggressive NK leukemia

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose of everolimus in combination with bortezomib

    Defined as the highest dose level at which 0 out of 3, or 1 out of 6, subjects experiences dose-limiting toxicity (DLT).

    after 1 course (21 days)

Secondary Outcomes (5)

  • Frequency counts and percentage of patients experiencing toxicities

    After 1 course (21 days)

  • Pharmacokinetics

    after 1 course (21 days)

  • Response rate

    Every 3 courses (9 weeks) for the first 12 courses, after 5th restaging scan every 6 courses (18 weeks) until off study

  • 6-month progression-free survival

    6 months

  • Correlation of tumor characteristics with response to treatment

    after one course (21 days)

Study Arms (1)

Everolimus and Bortezomib

EXPERIMENTAL

Patients will receive a combination of Everolimus by mouth and Bortezomib intravenously for a 21 day cycle.

Drug: BortezomibDrug: Everolimus

Interventions

BortezomibDRUG

Patients will be assigned to one of the following dose levels of Bortezomib: 0.7mg/m2, 1.0 mg/m2, or 1.3mg/m2 on days 1,4,8,11 of a 21 day cycle. The appropriate amount of bortezomib will be drawn from the injection vial and administered as an intravenous (IV) push or sub-cutaneously over 3 to 5 seconds followed by a standard saline flush or through a running IV line.

Also known as: Velcade
Everolimus and Bortezomib
EverolimusDRUG

Everolimus 5 mg PO every other day, 5 mg by mouth (PO) daily, or 10 mg PO daily

Also known as: RAD001
Everolimus and Bortezomib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Able to provide voluntary written informed consent, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Diagnosed with relapsed or refractory NHL, limited to subtypes listed below. The subject must have histologic information of diagnosis according to review at the Cleveland Clinic Foundation, either at initial diagnosis or at any subsequent relapse. (Biopsy is not required at relapse, but is suggested. Biopsy at outside institution, reviewed at the Cleveland Clinic, is acceptable.)
  • "Relapsed or refractory" refers to patients who have received at least 1 prior treatment regimen for lymphoma (which may include prior autologous stem cell transplantation) and have demonstrated evidence of progressive disease by clinical and/or radiographic characteristics.
  • "Indolent lymphoma" is included, and refers to small lymphocytic lymphoma/B-cell chronic lymphocytic leukemia (SLL/CLL); lymphoplasmacytic lymphoma (with or without Waldenstrom's macroglobulinemia); hairy cell leukemia; follicular lymphoma (FL) of any grade; marginal zone B-cell lymphoma; or mantle cell lymphoma.
  • Transformed lymphoma is included if patients are ineligible for (or refuse) hematopoetic stem cell transplant.
  • In addition, cutaneous B and T cell lymphoma are permitted. Cutaneous T cell lymphoma must be refractory to 1 prior systemic therapy (topical therapy, photopheresis, radiation are not considered systemic therapy). Transformed B and T cell cutaneous lymphoma are also permitted.
  • Relapsed/refractory diffuse large B cell lymphoma (DLBCL) is allowed if the patient is not eligible for, or refuses, hematopoetic stem cell transplant.
  • Relapsed/refractory nodal, leukemic, and extranodal T cell lymphomas are eligible. Subtypes eligible include anaplastic large cell lymphoma, angioimmunoblastic T cell lymphoma, PTCL-NOS, nasal or disseminated extranodal T/NK lymphoma, enteropathy-associated T cell lymphoma, hepatosplenic gamma/delta T cell lymphoma, subcutaneous panniculitis-like T cell lymphoma, T-prolymphocytic leukemia, Adult T-cell leukemia/lymphoma, large granular lymphocytic leukemia, aggressive NK leukemia.
  • Plasma cell myeloma and Hodgkin lymphoma are excluded.
  • Prior therapy with bortezomib is allowed. Patients who have received prior bortezomib therapy must have received bortezomib \>6 months ago, and must have shown some response. Patients that did not respond to prior bortezomib therapy are not eligible.
  • Measurable disease by one of the following: radiographic criteria (≥2 cm by computed tomography); lymphoma involving peripheral blood with more than 5000 leukemia cells/mm3, or any degree of bone marrow infiltration on bone marrow biopsy. Skin involvement with or without nodal or bone marrow involvement permitted for cutaneous lymphomas is also permitted. (see section 6.0, Measurement of Effect).
  • Eastern Cooperative Group (ECOG) Performance Status of 0-2.
  • Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. Serum AST or serum ALT levels must be ≤2.5 x ULN, or ≤5 x ULN for patients with liver involvement by lymphoma.
  • Must have adequate bone marrow function:
  • Absolute neutrophil count (ANC) ≥1,000/uL
  • +12 more criteria

You may not qualify if:

  • Prior treatment with any investigational drug, chemotherapy, or monoclonal antibody within the preceding 1 month
  • Chronic treatment with systemic steroids or another immunosuppressive agent.
  • Patients should not receive immunization with attenuated live vaccines during study period.
  • History of allogeneic stem cell transplantation.
  • Any patient with known diabetes mellitus currently requiring insulin therapy, or any patient with preexisting diabetes mellitus in poor control, defined as a hemoglobin A1C (HbA1C) value of over 9% within 4 weeks of starting therapy
  • Fasting serum cholesterol \>300 mg/dL OR \>7.75 mmol/L or fasting triglycerides \> 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or low-risk prostate cancer after curative therapy.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • unstable angina pectoris, any history of congestive heart failure, any history of known myocardial infarction, uncontrolled cardiac arrhythmia
  • severely impaired lung function
  • uncontrolled diabetes as defined by fasting serum glucose \>1.5x ULN, off medications
  • any active (acute or chronic) or uncontrolled infection/ disorders.
  • nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
  • liver disease including a known history of viral hepatitis B or C, evidence of cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

LymphomaLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaLeukemia, Hairy CellLymphoma, T-CellLymphoma, T-Cell, CutaneousRecurrenceLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyEnteropathy-Associated T-Cell LymphomaSubcutaneous panniculitis-like T-cell lymphomaLeukemia, Prolymphocytic, T-CellPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLeukemia, Large Granular Lymphocytic

Interventions

BortezomibEverolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, Non-HodgkinLymphoma, B-CellLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphadenopathyLeukemia, ProlymphocyticLeukemia, T-CellPrecursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsSirolimusMacrolidesLactones

Study Officials

  • Brian Hill, MD, PhD

    Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

May 2, 2008

First Posted

May 5, 2008

Study Start

June 1, 2008

Primary Completion

October 1, 2015

Last Updated

October 28, 2015

Record last verified: 2015-10

Locations

US(1)