Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Waldenstrom Macroglobulinemia

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Patients receive oral perifosine (150 mg) daily each cycle. Cycle duration is 28 days. After cycle 2, response is assessed and patients with stable or responding disease can continue for another 4 cycles or until disease progression (PD). Protocol treatment duration is 6 cycles but patients may receive perifosine maintenance per investigator discretion in absence of PD.

Perifosine

Irene Ghobrial, MD

Waldenström's Macroglobulinemia (lymphoplasmacytic lymphoma, WM) remains incurable with limited therapeutic options and notably absent FDA approved therapy with any WM indication. Therefore, there is a need to identify new therapeutic agents for WM patients both in the upfront and relapsed/refractory setting. The purpose of this research study is to assess the efficacy of perifosine in patients with relapsed or refractory WM.

Perifosine is a drug that in particular inhibits Akt thought to be important for initiation and progression of malignancies, specifically in lymphomas. In laboratory experiments of WM and lymphoma cell lines, perifosine has shown to have cytotoxic and anti-proliferative activity as a single agent. This drug has been used in clinical research studies of other types of cancers including soft tissue sarcomas, head and neck cancers and prostate cancer. This study uses a two-stage design to evaluate efficacy of perifosine based on overall response (OR). The null and alternative OR rates are 20% and 40%. If 4 or more patients enrolled in the stage one cohort (n=17 patients) achieve OR than accrual will proceed to stage two (n=20 patients). If fewer than 10 ORs are observed then the regimen will be considered ineffective.

Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

A Phase II Study of Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

OR rate is the percentage of patients achieving Complete Response (CR), Partial Response (PR) or Minimal Response (MR) during treatment based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003). CR: Disappearance of serum monoclonal IgM protein (IgM M-protein) by immunofixation; no histologic evidence of bone marrow (BM) involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan); PR: At least 50% reduction of IgM M-protein and at least 50% decrease in adenopathy/organomegaly on physical examination or on CT scan; and MR: At least 25% but less than 50% reduction of IgM M-protein by protein electrophoresis. Patients must have no new symptoms or signs of active disease.

TTP estimated using the Kaplan-Meier method is defined as the time from registration to disease progression (PD) based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003) Patients without PD are censored at time of last disease assessment. PD: At least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed with a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease (i.e., anemia, thrombocytopenia, leucopenia, bulky adenopathy/organomegaly) or symptoms (unexplained recurrent fever of at least 38.4oC, drenching night sweats, at least 10% body weight less, or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis) attributable to WM.

PFS estimated using the Kaplan-Meier method is defined as the time from registration to death from any cause or disease progression (PD) based on criteria from the 2nd International Workshop on WM. (Weber D, Treon S, et al. Seminars in Oncology 2003) Patients alive without PD are censored at time of last disease assessment. PD: At least 25% increase in serum monoclonal IgM protein by electrophoresis confirmed with a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease (i.e., anemia, thrombocytopenia, leucopenia, bulky adenopathy/organomegaly) or symptoms (unexplained recurrent fever of at least 38.4oC, drenching night sweats, at least 10% body weight less, or hyperviscosity, neuropathy, symptomatic cryoglobulinemia, or amyloidosis) attributable to WM.

The percentage of patients experiencing treatment-related grade 3-4 adverse events based on CTCAEv3 as reported on case report forms.

Dana-Farber Cancer Institute

Principal Investigator

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Irene M. Ghobrial, MD

The analysis dataset is comprised of all enrolled patients.

Overall Response (OR) Rate

Time to Progression (TTP)

Progression Free Survival (PFS)

Treatment-Related Grade 3-4 Adverse Event Rate

Overall Study

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Bortezomib

Antineoplastic Agents, Immunological

Immunologic Factors

Intravenously once a week for the first and fourth weeks of a cycle

In this study, we are trying to find out if the combination of these two drugs is effective in treating Waldenstrom's macroglobulinemia (WM). The combination of these two drugs has not been studied for patients with relapsed or refractory macroglobulinemia. The U.S. Food and Drug Administration (FDA) has approved bortezomib for the treatment of multiple myeloma, a cancer that is closely related to Waldenstrom's macroglobulinemia.

* Participants will receive 6 cycles of the study treatment with bortezomib and rituximab. Each cycle is 28 days long (4 weeks).
* Participants will receive Rituximab intravenously once a week for the first and fourth cycles only. Participants will receive bortezomib once a week for three weeks on and one week off every cycle, for a total of 6 cycles.
* During the rituximab infusion, the participants blood pressure and pulse will be monitored frequently. The rate of infusion may be decreased depending upon the side effects that are experienced.
* Blood samples will be collected before the first dose and on follow up with every cycle. Blood counts will also be performed every week.
* Routine physical exams will be performed at each evaluation. A PET/CAT scan of the chest, abdomen and pelvis at the end of treatment. This scan is required to assess the response of the participants disease.
* In order to learn more on how bortezomib and rituximab affect WM, a bone marrow biopsy will be performed.
* We anticipate that participants will complete the active therapy over a period of 6 cycles provided that they are benefiting from therapy and have not had any serious side effects. The participant will be followed every three months for 2 years for office visits and laboratory tests.

Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)

Phase II Study of Combination Bortezomib (Velcade PS-341) and Rituximab in Patients With Previously Untreated and Relapsed/Refractory Waldenstrom's Macroglobulinemia

Overall Response Rate= Minor response (\>25%-50% reduction in monoclonal IgM from baseline + Partial Response (\>50-90% reduction in monoclonal IgM from baseline)+ Complete Response (Disappearance of monoclonal protein by immunofixation; no histologic evidence of bone marrow involvement, resolution of any adenopathy/organomegaly (confirmed by CT scan), or signs or symptoms attributable to WM. Reconfirmation of the CR status is required at least 6 weeks apart with a second immunofixation.)

Time to progresion is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum monoclonal IgM electrophoresis confirmed by a second measurement at least 2 weeks apart, or progression of clinically significant findings due to disease or symptoms attributable to WM.

Time from documentation of first response to progressive disease.

Millennium Pharmaceuticals, Inc.

bortezomib and rituximab

Bortezomib: Once weekly for 3 weeks

Rituximab: Intravenously once a week for the first and fourth weeks of a cycle

Bortezomib and Rituximab

Age, Categorical

Irene M. Ghobrial

Patients who had received at least one prior line of therapy

Overall Response Rate of Bortezomib and Rituximab (VR) in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (WM)

Participants who were previously untreated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia	NCT00422656	Waldenstrom's M...	Perifosine	18 Years -	Dana-Farber Cancer Institute
Combination Bortezomib and Rituximab in Patients With Waldenstrom's Macroglobulinemia (WM)	NCT00422799	Waldenstrom's M...	Bortezomib Rituximab	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for relapsed waldenstrom's macroglobulinemia