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

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT01164709

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Trial of Nelfinavir and Bortezomib in Advanced Hematologic Malignancies

Study Start Date :

Jul 1, 2010

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bortezomib + nelfinavir escalation 3 by 3 cohorts	Drug: bortezomib Bortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2 Other Names: Velcade Drug: nelfinavir mesylate p.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d Other Names: Viracept

Arm

Intervention/Treatment

Experimental: bortezomib + nelfinavir

escalation 3 by 3 cohorts

Drug: bortezomib

Bortezomib i.v., day 8, 11, 15, 18; 1.3 mg/m2

Other Names:

Velcade

Drug: nelfinavir mesylate

p.o., days 1 to 21; dose level: (625), 1250, 1875, or 2500 mg, 2x/d

Other Names:

Viracept

Outcome Measures

Primary Outcome Measures

Dose limiting toxicity [during first cycle]

Secondary Outcome Measures

Objective response [during treatment]
Adverse events according to NCI CTCAE v.4.0 [during treatment + 30 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	Inselspital Bern	Bern	Switzerland	CH-3010
2	Kantonsspital Graubuenden	Chur	Switzerland	CH-7000
3	Centre Hospitalier Universitaire Vaudois	Lausanne	Switzerland	CH-1011
4	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