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

Lymphoma Clinical Trial

Official title:

Phase I Trial of Nelfinavir and Bortezomib in Advanced Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164709
• Other study ID #: SAKK 65/08
• Secondary ID: SWS-SAKK-65/08EU
• Status: Completed
• Phase: Phase 1
• Start date: July 2010
• Est. completion date: November 2013

Study information

• Verified date: May 2019
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2013
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Mature T-cell and Nk-cell Neoplasms
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Drug:
• bortezomib
Bortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2
• nelfinavir mesylate
p.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d

Locations

Country	Name	City	State
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital - St. Gallen	St. Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Driessen C, Kraus M, Joerger M, Rosing H, Bader J, Hitz F, Berset C, Xyrafas A, Hawle H, Berthod G, Overkleeft HS, Sessa C, Huitema A, Pabst T, von Moos R, Hess D, Mey UJ. Treatment with the HIV protease inhibitor nelfinavir triggers the unfolded protein — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity		during first cycle
Secondary	Objective response		during treatment
Secondary	Adverse events according to NCI CTCAE v.4.0		during treatment + 30 days