S0629, Observation or Combination Chemotherapy, Bortezomib, Thalidomide, and Rituximab Followed By Two Autologous Peripheral Blood Stem Cell Transplants in Treating Patients With Waldenstrom Macroglobulinemia

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. Giving combination chemotherapy together with bortezomib, thalidomide, and rituximab before an autologous peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This observational and phase II trial is studying how well giving combination chemotherapy together with bortezomib, thalidomide, and rituximab followed by two autologous peripheral blood stem cell transplants works in treating patients with Waldenstrom macroglobulinemia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bortezomib; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Etoposide phosphate; Liposomal doxorubicin; Melphalan; Rituximab; Thalidomide

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of Waldenstrom macroglobulinemia (WM)

• Measurable disease as determined by IgM protein quantification

• Must be registered to the treatment portion of the study within 28 days of experiencing disease-related symptoms* AND must present with ≥ 1 of the following disease-related symptoms:

• Hemoglobin ≤ 11 g/dL

• Platelet count ≤ 100,000/mm³

• Marked tumor mass, defined as lymphadenopathy > 2 cm, palpable hepatomegaly, splenomegaly, or significant marrow involvement (> 50%)

• Serum albumin < 2.5 g/dL

• Persistently elevated beta-2-microglobulin > 3.0 mg/L in the absence of renal impairment or active infections

• Presence of B symptoms (i.e., fever, night sweats, or weight loss of > 10% from baseline)

• Appearance of new or worsening neuropathy manifested by numbness and tingling or pain

• Symptomatic cryoglobulinemia (i.e., Raynaud phenomenon, skin ulcers, cold urticaria, or skin necrosis)

• Symptoms of hyperviscosity, if measured viscosity > 4 cp (i.e., new headaches, vertigo, ataxia, dizziness with or without evident causes of changes in funduscopic exam, including retinal vein engorgement, hemorrhages, or exudates)

• NOTE: *Appearance of any of the above symptoms caused by WM with no other obvious cause is a trigger for treatment initiation. Symptoms need not persist for any specified time frame.

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2 (Zubrod performance status 3 allowed provided it is based solely on morbidity due to WM)

• ANC > 1,500/mm³ (unless more marked cytopenias can be explained by marked marrow involvement or autoimmune myelosuppression)

• Serum creatinine < 3 mg/dL

• Creatinine clearance > 30 mL/min

• SGOT/SGPT < 2 times upper limit of normal

• Direct bilirubin < 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception according to the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program

• Ejection fraction ≥ 50% by ECHO or MUGA scan

• Patients with evidence of amyloidosis (i.e., periorbital perforation, proteinuria not attributable to Bence-Jones protein, unexplained arrhythmias, increased liver function tests, peripheral neuropathy, carpal tunnel syndrome, and/or macroglossia) must have an ECHO, rather than MUGA, performed to evaluate for cardiac amyloidosis (septal thickness, diastolic dysfunction, granular sparkling, or low-voltage QRS complexes)

• No myocardial infarction within the past 6 months

• No unstable angina

• No difficult-to-control congestive heart failure or cardiac arrhythmias

• No uncontrolled hypertension

• No peripheral neuropathy ≥ grade 2

• No history of multi-infarced dementia or multiple strokes

• No known hypersensitivity to boron or mannitol

• No hepatitis B or C positivity

• No HIV positivity

• No other prior malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• At least 28 days since prior chemotherapy and/or radiotherapy and recovered

• No prior bortezomib

• No concurrent glucocorticoids unless used to control autoimmune disease associated with WM

• Concurrent participation in the Myeloma Specimen Repository study allowed