Nelfinavir Mesylate and Bortezomib in Treating Patients With Relapsed or Progressive Advanced Hematologic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01164709
First received: July 16, 2010
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

RATIONALE: Nelfinavir mesylate and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of hematologic cancer by blocking blood flow to the cancer. Giving nelfinavir mesylate together with bortezomib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir mesylate when given together with bortezomib in treating patients with relapsed or progressive advanced hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Mature T-cell and Nk-cell Neoplasms
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: nelfinavir mesylate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Nelfinavir and Bortezomib in Advanced Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: during first cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response [ Time Frame: during treatment ] [ Designated as safety issue: No ]
  • Adverse events according to NCI CTCAE v.4.0 [ Time Frame: during treatment + 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: July 2010
Study Completion Date: November 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bortezomib + nelfinavir
escalation 3 by 3 cohorts
Drug: bortezomib
Bortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2
Other Name: Velcade
Drug: nelfinavir mesylate
p.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d
Other Name: Viracept

Detailed Description:

OBJECTIVES:

  • To assess the safety of nelfinavir mesylate in combination with bortezomib in patients with relapsed or progressive, advanced hematologic malignancies.
  • To establish the phase II recommended dose of nelfinavir mesylate in these patients.

OUTLINE: This is a multicenter, dose-escalation study of nelfinavir mesylate.

Patients receive oral nelfinavir mesylate twice daily on days 1-21 and bortezomib IV on days 8, 11, 15, and 18 in course 1. Course 1 has a duration of 28 days. Beginning in course 2, patients receive oral nelfinavir mesylate twice daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days for 2 courses. Patients with responding disease may continue to receive nelfinavir mesylate and bortezomib for up to 4 additional courses.

After completion of study treatment, patients are followed for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosed with advanced hematologic malignancies meeting the following criteria:

    • Multiple myeloma

      • Received ≥ 2 lines of prior chemotherapy (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
    • Acute myeloid leukemia
    • Acute lymphoblastic leukemia
    • Diffuse large B-cell lymphoma
    • Hodgkin lymphoma
    • Mantle cell lymphoma
    • Mature T- and NK-cell neoplasms restricted to the following WHO-defined entities:

      • T-cell prolymphocytic leukemia
      • T-cell large granular lymphocytic leukemia
      • Aggressive NK-cell leukemia
      • Adult T-cell leukemia/lymphoma
      • Extranodal NK/T-cell lymphoma (nasal type)
      • Mycosis fungoides
      • Sézary syndrome
      • Primary CD30-positive T-cell lymphoproliferative disorders
      • Primary cutaneous anaplastic large cell lymphoma
      • Primary cutaneous gamma-delta T-cell lymphoma
      • Peripheral T-cell lymphoma (not otherwise specified)
      • Angioimmunoblastic T-cell lymphoma
      • Anaplastic large cell lymphoma (ALK-positive/ALK-negative)
    • Grade 3B follicular lymphoma
  • Relapsed following or progressed during standard therapy
  • Meeting the following criteria:

    • Standard intensive therapy is not feasible
    • Current disease state for which there is no standard effective therapy
    • Refused standard therapy where no curative option exists
  • Measurable disease, defined as the following:

    • Myeloma: measurable serum monoclonal protein > 1 g/dL for IgG, or > 0.5 g/dL for IgA, IgM or IgD, or difference between involved and uninvolved free light chain levels in serum > 100 mg/L
    • Lymphoma: must have ≥ 1 lesion measurable by CT (longest diameter ≥ 15 mm)
    • Acute leukemia: ≥ 20% blasts in bone marrow or in peripheral blood (≥ 200/mL blasts in peripheral blood)
  • No HIV-associated lymphoma

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³ (if bone marrow impairment, ≥ 20,000/mm^3)
  • Hemoglobin > 80 g/L (if considered to be caused by the underlying hematologic malignancy or bone marrow impairment, > 80 g/L after transfusion)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) (if suspected hemolysis, direct bilirubin ≤ 1.5 times ULN)
  • ALT ≤ 2.5 times ULN
  • Calculated creatinine clearance > 30 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study treatment
  • Willing and capable to comply with an oral regimen
  • Capable of understanding information given by the investigator on the trial
  • Able to adhere and remain in geographic proximity to allow proper staging, treatment, and followup
  • No other non-hematologic malignancy within the past 5 years, except adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
  • No known chronic hepatitis B or C infection or known HIV infection
  • No serious underlying medical condition (at the judgment of the investigator) which would impair the ability of the patient to participate in the trial, including any of the following:

    • Active autoimmune disease
    • Uncontrolled diabetes
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric disorder
  • No myocardial infarction within the past 6 months
  • No polyneuropathy > grade 1 significantly interfering with activities of daily living or painful polyneuropathy
  • No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No more than 4 prior lines of chemotherapeutic regimens (induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant with or without maintenance therapy is considered one line of therapy)
  • More than 30 days since prior treatment in a clinical trial
  • More than 30 days since prior and no concurrent chemotherapy or biologic agents

    • For patients with acute leukemia, hydroxyurea may be given up to 48 hours before first administration of the trial treatment, and low dose cytarabine (up to 20 mg/m^2) and mitoxantrone up to 20 mg up to 14 days before first dosing
  • At least 1 week since prior and no concurrent CYP3A4 modulators
  • No concurrent other experimental drugs
  • No concurrent radiotherapy
  • No concurrent antineoplastic therapy with chemotherapeutic or biologic agents
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01164709

Locations
Switzerland
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH-1011
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Christoph Driessen, MD Cantonal Hospital of St. Gallen
Principal Investigator: Dagmar Hess, MD Cantonal Hospital of St. Gallen
Principal Investigator: Roger von Moos, MD Kantonsspital Graubuenden
Principal Investigator: Thomas Pabst, MD University Hospital Inselspital, Berne
  More Information

No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01164709     History of Changes
Other Study ID Numbers: SAKK 65/08, SWS-SAKK-65/08, EU-21051, SWS-SAKK-JC26866138LYM1005, CDR0000681442
Study First Received: July 16, 2010
Last Updated: January 31, 2014
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
refractory multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult diffuse large cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent mantle cell lymphoma
recurrent adult T-cell leukemia/lymphoma
adult nasal type extranodal NK/T-cell lymphoma
angioimmunoblastic T-cell lymphoma
peripheral T-cell lymphoma
T-cell large granular lymphocyte leukemia
anaplastic large cell lymphoma
recurrent grade 3 follicular lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
aggressive NK-cell leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
secondary acute myeloid leukemia
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma
Leukemia
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Nelfinavir
Bortezomib
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014