Clinical trial NCT01813227
Conditions: Waldenstrom Macroglobulinemia
Sponsor: Hackensack Meridian Health
Start date: 2013-04-01; Completion date: 2018-10-01
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the safety and effectiveness of an investigational study drug called carfilzomib. The investigators want to find out what effects, good and/or bad, it has on patients and their cancer if treatment continues beyond previous carfilzomib treatment study.

Carfilzomib (KyprolisTM) is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. It has not been approved to be used for any other disease or condition.

In this study, carfilzomib is referred to as an investigational study drug because it is not approved for use in all patients with multiple myeloma in the United States, and it is not approved by some regulatory authorities (the agencies that are responsible for approving the use of a medicine in a country such as Health Canada).

Carfilzomib is a type of drug called a proteasome inhibitor. A proteasome is a protein found within cells that has the important role of identifying and marking damaged proteins that are needed to be destroyed by the cell for survival. The inhibition of the proteasome allows for damaged protein to accumulate within cells. This accumulation of damaged protein causes the cell to die.

Detailed description:
Waldenström's macroglobulinemia (WM) is a rare low-grade B-cell lymphoplasmacytic lymphoma. Overall reported incidences approximately 3 cases per million persons per year with about 1500 and cases diagnosed annually in United States. There is a higher incidence in males compared to females (3.4 vs 1.7 cases per 1 million person-years at risk) and WM is nearly twice as common among whites compared to blacks.\[1\] A familial form of the disease is also recognized. WM is an indolent disease with an overall median survival of 5 years although more recent data suggest a disease-specific median survival of 11.2 years, given the frequently older age (median 63 years) and accompanying co-morbidities at diagnosis(1). WM is characterized by infiltration of lymphoplasmacytic cells and bone marrow and by serum immunoglobulin M (IgM) monoclonal gammopathy. B-cell origin and some clinical cellular and epidemiological features are shared among WM arises from intermediately mature B cells (somatically mutated post germinal center the lymphocytes that have not yet undergone isotype switching), as opposed to immature B cells from which chronic lymphocytic leukemia arises in the fully mature, somatically mutated, from which cells multiple myeloma arises.

There is no standard of care for WM (2). Therefore, involving the patient's in clinical trials is strongly recommended whenever possible.

Arms: arm 1: Carfilzomib 20 mg/m2 on day 1, 2 then 56 mg/m2 days 8, 9 and 15, 16 over 30 minutes every 28 days. Dexamethasone 4 mg (8 mg if \> 45 mg/m2) orally each day of carfilzomib therapy. If less than a partial remission (PR) after 4 cycles, add rituximab 375 mg/m2 on day 16 of each cycle. Patients who meet the criteria for progression prior to 4 cycles of therapy will have rituximab added to their treatment. For patients receiving rituximab, the carfilzomib dose will be decreased to 27 mg/m2. Patients will be treated to maximal response plus 2 additional cycles to a maximum of 12 cycles.
Interventions: intervention 1: Carfilzomib intervention 2: Rituximab intervention 3: Dexamethasone
Intervention descriptions: intervention 1: If you decide to participate in the study, you will receive carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days for a minimum of 2 cycles (approximately 2 months). You may receive additional cycles for as long as your disease remains stable or improved or until your study doctor determines that you should stop receiving the study drug or you decide to stop participating in the study. intervention 2: If you decide to participate in the study, in addition to the carfilzomib and possible dexamethasone administration, If less than a partial remission (PR) after 4 cycles is achieved, rituximab 375 mg/m2 on day 16 of each subsequent cycle will be added to the treatment. Subjects who meet the criteria for progression prior to 4 cycles of therapy will have rituximab 375 mg/m2 weekly for 4 consecutive weeks every 3 cycles added to the treatment. Subjects will be treated to maximal response plus 2 additional cycles to a maximum of 12 cycles.

At the beginning of every cycle, your study doctor will see if your general health is satisfactory. You will be asked to report any side effects or problems you have had since the start of the last treatment cycle as well as any medication change(s). intervention 3: If you decide to participate in the study, you will receive carfilzomib on Days 1, 2, 8, 9, 15, and 16 every 28 days for a minimum of 2 cycles (approximately 2 months). You may receive additional cycles for as long as your disease remains stable or improved or until your study doctor determines that you should stop receiving the study drug or you decide to stop participating in the study.

You will also receive dexamethasone weekly on Days 1, 2, 8, 9, 15 and 16 starting with cycle 1 and continuing every cycle thereafter.

Protocol documents: