Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia

NCT00492050 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 2005-0733NCI-2012-01498
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab

  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. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed.Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.

  After 2 (35 day) cycles of treatment

• Response Rate After 3 Cycles of Treatment With Bortezomib and Rituximab

  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. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed. Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.

  After 3 (35 day) cycles of treatment

• Participants Ability to Collect Stem Cells After Treatment With Bortezomib and Rituximab

  Number of Participants who were able to collect stem cells successfully or unable to collect after treatment with bortezomib and rituximab.

  4 weeks

Study Arms (1)

Bortezomib + Rituximab

EXPERIMENTAL

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; Drug: Rituximab; Drug: Valacyclovir

Interventions

Bortezomib DRUG

1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22.

Also known as: Velcade, LDP-341, MLN341, PS-341

Bortezomib + Rituximab

Rituximab DRUG

375 mg/m\^2 IV on Day 8 and 22.

Also known as: Rituxan

Bortezomib + Rituximab

Valacyclovir DRUG

500 mg orally daily (or acyclovir 200 mg orally twice daily)

Also known as: Valtrex

Bortezomib + Rituximab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• 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.
• Patient has a heart rate (HR) of greater than or equal to 50 bpm.

You may not qualify if:

• 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.
• 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.
• 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).
• Patient has \>/= Grade 2 peripheral neuropathy on baseline evaluation.
• 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.
• Patient has hypersensitivity to boron, mannitol, or murine proteins.
• 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.
• Patient has received other investigational drugs within 14 days before enrollment
• Patient has a serious medical or psychiatric illness that is likely to interfere with participation in this clinical study.
• Eastern Cooperative Oncology Group (ECOG) performance status of \> 2.
• 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.
• Patient with a lifetime cumulative dose of \> 450 mg/m\^2 of anthracyclines.
• Patients with an active hepatitis B infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Bortezomib; Rituximab; Valacyclovir

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Sheeba Thomas, MD-Professor, Lymphoma-Myeloma
• Organization: UT MD Anderson Cancer Center

sthomas@mdanderson.org

(713) 792-2860

Study Officials

• Sheeba Thomas, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2007
• First Posted: June 27, 2007
• Study Start: August 2, 2006
• Primary Completion: February 28, 2021
• Study Completion (Estimated): June 28, 2026
• Last Updated: March 11, 2026
• Results First Posted: May 4, 2022

Record last verified: 2026-02

Locations

US (1)