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S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease

Phase 2
18 Years
Not Enrolling

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Trial Information

S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease



- To assess the progression-free and overall survival of patients with symptomatic
Waldenstrom macroglobulinemia treated with bortezomib, dexamethasone, thalidomide,
cisplatin, doxorubicin hydrochloride, cyclophosphamide, and etoposide (VDT-PACE) in
combination with rituximab, followed by single or tandem autologous peripheral blood
stem cell transplantation and maintenance therapy.

- To assess the confirmed and unconfirmed response in patients treated with this regimen.


- To evaluate the feasibility and toxicity of this regimen in these patients.

- To correlate the time to symptom development and overall survival with standard
prognostic factors and cytopenias.

- To examine the natural history of Waldenstrom macroglobulinemia.

- To identify, in a preliminary fashion, biological correlates that may relate to
progression or to symptomatic disease.

OUTLINE: This is a multicenter study. Patients with asymptomatic disease at study entry
proceed directly to observation. Patients with symptomatic disease at study entry proceed
directly to induction therapy.

- Observation: Patients with asymptomatic disease undergo observation monthly for 3
months and then every 3 months for up to 3 years. Patients who develop symptomatic
disease proceed to induction therapy within 28 days of onset of disease symptoms.
Patients who continue to have asymptomatic disease after 3 years of observation are
removed from the study.

- Induction therapy: Patients receive oral dexamethasone and oral thalidomide on days
1-4; cisplatin IV, doxorubicin hydrochloride IV, cyclophosphamide IV, and etoposide IV
continuously on days 1-4; bortezomib IV on days 1, 4, 8, and 11; and rituximab IV on
days 1, 8, and 15. Treatment repeats every 6-8 weeks for 2 courses in the absence of
disease progression or unacceptable toxicity.

- Peripheral blood stem cell (PBSC) collection: Patients receive filgrastim (G-CSF) IV
beginning on day 9 of course 1 of induction therapy and continuing until WBC counts are
adequate for apheresis. Patients also receive G-CSF IV beginning on day 6 of course 2
of induction therapy and continuing until apheresis is complete.

- First autologous PBSC transplantation*: Beginning approximately 4-6 weeks after the
completion of induction therapy, patients receive conditioning therapy comprising
high-dose melphalan IV and bortezomib IV on days -4 and -1. Patients undergo autologous
PBSC transplantation on day 0 NOTE: *Patients who will receive a single transplant (for
medical, insurance, or other reasons) will not receive melphalan and bortezomib, but
will receive conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM)
and will proceed to Maintenance Therapy.

- Second autologous PBSC transplantation: Beginning approximately 56-90 days after the
first transplant, patients receive conditioning therapy comprising carmustine IV over 2
hours on day -5; etoposide IV over 1 hour and cytarabine IV over 1 hour on days -5 to
-2; and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day

- Maintenance therapy: Beginning after platelet counts recover, patients receive
bortezomib IV on days 1, 4, 8, and 11 and rituximab IV over 2 hours on day 11.
Treatment repeats every 3 months for 2 years in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for up to 5 years.

Inclusion Criteria


- 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

- Appearance of new or worsening neuropathy manifested by numbness and tingling or

- 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.


- 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


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival at 3 years

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Gordan Srkalovic, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Sparrow Regional Cancer Center


United States: Federal Government

Study ID:




Start Date:

September 2008

Completion Date:

Related Keywords:

  • Lymphoma
  • Waldenström macroglobulinemia
  • Lymphoma
  • Waldenstrom Macroglobulinemia



Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201
Hurley Medical Center Flint, Michigan  48503
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Genesys Hurley Cancer Institute Flint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
St. John Macomb Hospital Warren, Michigan  48093
CCOP - Dayton Kettering, Ohio  45429
Wesley Medical Center Wichita, Kansas  67214
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove, Indiana  46107
Grandview Hospital Dayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley Hospital Dayton, Ohio  45409
Good Samaritan Hospital Dayton, Ohio  45406
Blanchard Valley Medical Associates Findlay, Ohio  45840
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Middletown Regional Hospital Middletown, Ohio  45044
UVMC Cancer Care Center at Upper Valley Medical Center Troy, Ohio  45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia, Ohio  45385
Reid Hospital & Health Care Services Richmond, Indiana  47374
Lawrence Memorial Hospital Lawrence, Kansas  66044
Foote Memorial Hospital Jackson, Michigan  49201
St. Mary Mercy Hospital Livonia, Michigan  48154
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Clinton Memorial Hospital Wilmington, Ohio  45177