Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia

Study Description

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Brief Summary:

The main goal of this clinical research study is to learn if Velcade ® (bortezomib) given with rituximab can help to control WM. This drug combination will allow researchers to collect your stem cells in case it is possible to transplant the stem cells as treatment if your WM gets worse. Researchers will also look at the safety and tolerability of this drug combination followed by treatment with other drug combinations.

Condition or disease	Intervention/treatment	Phase
Waldenstrom's Macroglobulinemia	Drug: Bortezomib; Drug: Rituximab; Drug: Valacyclovir	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	38 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Primary Treatment of Waldenstrom's Macroglobulinemia With Bortezomib (Velcade) and Rituximab (Rituxan) Followed by Autologous Stem Cell Collection
Actual Study Start Date :	August 2006
Estimated Primary Completion Date :	February 2020
Estimated Study Completion Date :	February 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Bortezomib + Rituximab; Bortezomib 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily).	Drug: Bortezomib; 1.6 mg/m^2 IV Weekly on Days 1, 8, 15 and 22.; Other Names: Velcade; LDP-341; MLN341; PS-341 Drug: Rituximab; 375 mg/m^2 IV on Day 8 and 22.; Other Name: Rituxan Drug: Valacyclovir; 500 mg orally daily (or acyclovir 200 mg orally twice daily); Other Name: Valtrex

Outcome Measures

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Primary Outcome Measures :

1. Overall response rate to Bortezomib-Rituximab, and autologous stem cell collection rate after induction therapy with Bortezomib-Rituximab [ Time Frame: Within 1 week prior to the start of each cycle of chemotherapy and every 3 months thereafter until Partial Recovery (PR) achieved ]

   The method of Thall, Simon, Estey (1995, 1996) as extended by Thall and Sung (1998) used for trial monitoring.

   Partial response (PR) defined as at least > 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, > 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease.

   Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography [CT] scan), and no signs or symptoms attributable to WM.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Patients with symptomatic macroglobulinemic lymphoma who have had no prior treatment, or whose prior treatment has been limited to steroids and/or alpha-interferon, are eligible. Macroglobulinemic lymphoma includes patients with either biopsy proven clonal lymphocytic or lymphoplasmacytic proliferation and monoclonal IgM. Also included are symptomatic patients with clonal proliferation producing a pathologic monoclonal IgM that causes cryoglobulinemia, peripheral neuropathy or cold agglutinin hemolytic anemia.
2. Patients must have acceptable liver function (total bilirubin < 2.5mg/dL) and renal function (creatinine < 2.0mg/dL). Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass) that might reverse with improvement of disease.
3. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
4. Male subject agrees to use an acceptable method for contraception for the duration of the study.
5. Patients must voluntarily sign an informed consent form indicating that they are aware of the investigational nature of the study, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future care.
6. Patient has a heart rate (HR) of greater than or equal to 50 bpm.

Exclusion Criteria:

1. Patient has a platelet count of <30x10^9/L within 28 days before enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma or splenomegaly.
2. Patient has an absolute neutrophil count of <1.0x10^9/L within 28 days before enrollment unless due to >/= 75% marrow infiltration by macroglobulinemic lymphoma.
3. Patient has a calculated or measured creatinine >/= to 2.0mg/dL on baseline evaluation. Patients with impaired renal function will only be included if the renal failure is secondary to macroglobulinemic lymphoma (i.e. Bence Jones proteinuria, cryoglobulinemia, ureteral obstruction due to mass).
4. Patient has >/= Grade 2 peripheral neuropathy on baseline evaluation.
5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
6. Patient has hypersensitivity to boron, mannitol, or murine proteins.
7. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urine Beta -human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
8. Patient has received other investigational drugs within 14 days before enrollment
9. Patient has a serious medical or psychiatric illness that is likely to interfere with participation in this clinical study.
10. Eastern Cooperative Oncology Group (ECOG) performance status of > 2.
11. Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years and are considered by their physician to be at less than 30 % risk of relapse.
12. Patient with a lifetime cumulative dose of > 450 mg/m^2 of anthracyclines.
13. Patients with an active hepatitis B infection.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Millennium Pharmaceuticals, Inc.

Investigators

Principal Investigator:	Sheeba Thomas, MD	M.D. Anderson Cancer Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00492050 History of Changes
Other Study ID Numbers:	2005-0733; NCI-2012-01498 ( Registry Identifier: NCI CTRP )
First Posted:	June 27, 2007
Last Update Posted:	January 9, 2018
Last Verified:	January 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by M.D. Anderson Cancer Center:

Waldenstrom's Macroglobulinemia; Macroglobulinemic Lymphoma; Stem Cell Collection; Bortezomib; LDP-341	MLN341; PS-341; Velcade; Rituximab; Rituxan

Additional relevant MeSH terms:

Waldenstrom Macroglobulinemia; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders	Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Bortezomib; Valacyclovir; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antiviral Agents; Anti-Infective Agents