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

This study has been withdrawn prior to enrollment.
(lack of accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00723658
First received: July 26, 2008
Last updated: January 9, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: bortezomib
Drug: carmustine
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: melphalan
Drug: thalidomide
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: S0629, Observational Study of Asymptomatic Waldenstrom's Macroglobulinemia and Phase II Study of Tandem Autologous Transplant and Maintenance Treatment for Patients With Symptomatic Disease

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Progression-free survival at 3 years [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Response rate (complete response, very good partial response, and partial response) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Standard prognostic factors and other potential correlates that may relate to progression, symptomatic disease, and/or survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: September 2008
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Observation
Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.
Experimental: Treatment

Symptomatic pts: 2 cycles VTDPACE+R:

dex 40 mg PO D1-4 thalid 200 mg PO D1-4 cisplatin 10 mg/m2 IV D1-4 dox 10 mg/m2 IV D1-4 cyclophos 400 mg/m2 IV D1-4 etoposide 40 mg/m2 IV D1-4 bortezomib 1.0 mg/m2 IV D1,4,8,11 ritux 375 mg/m2 IV D1,8,15 lovenox 40 mg/d SQ D1-platelets >50,000/mcl GCSF 10 mcg/kg/d IV D9-WBC <2,000/mcl apheresis >/= 20x10^6 when WBC and CD34 within normal range, up to 4 cycles

  1. st Trans: mel 200 mg/m2 IV D-1 bortezomib 1.3 mg/m2 IV D-4, -1 PBSC >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 500 ml IV D-1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1
  2. nd Trans: BCNU 300 mg/m2 IV D-5 etoposide 200 mg/m2 IV D-5 to -2 AraC 400 mg/m2 IV D-5 to -2 mel 140 mg/m2 IV D-1 PBSC infusion >/=3.0x10^6/kg CD34 cells IV D0 GCSF 5 mcg/kg/d SQ D6-WBC recovery D5NS 150 ml/hr IV D-5 to -1 dex 40 mg/d PO D-4 to -1 ondansetron 24 mg OR granisetron 2 mg PO D-1
Biological: rituximab Drug: bortezomib Drug: carmustine Drug: cisplatin Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: melphalan Drug: thalidomide Procedure: autologous-autologous tandem hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 0.
  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723658

Locations
United States, Connecticut
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Indiana
St. Francis Hospital and Health Centers - Beech Grove Campus
Beech Grove, Indiana, United States, 46107
Reid Hospital & Health Care Services
Richmond, Indiana, United States, 47374
United States, Kansas
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Wesley Medical Center
Wichita, Kansas, United States, 67214
United States, Michigan
Saint Joseph Mercy Cancer Center
Ann Arbor, Michigan, United States, 48106-0995
CCOP - Michigan Cancer Research Consortium
Ann Arbor, Michigan, United States, 48106
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Dearborn, Michigan, United States, 48123-2500
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Genesys Hurley Cancer Institute
Flint, Michigan, United States, 48503
Hurley Medical Center
Flint, Michigan, United States, 48503
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
Foote Memorial Hospital
Jackson, Michigan, United States, 49201
Sparrow Regional Cancer Center
Lansing, Michigan, United States, 48912-1811
St. Mary Mercy Hospital
Livonia, Michigan, United States, 48154
St. Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, United States, 48060
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, United States, 48601
St. John Macomb Hospital
Warren, Michigan, United States, 48093
United States, Ohio
CCOP - Dayton
Dayton, Ohio, United States, 45420
Grandview Hospital
Dayton, Ohio, United States, 45405
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
Blanchard Valley Medical Associates
Findlay, Ohio, United States, 45840
Middletown Regional Hospital
Franklin, Ohio, United States, 45005-1066
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373-1300
Clinton Memorial Hospital
Wilmington, Ohio, United States, 45177
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Gordan Srkalovic, MD, PhD Sparrow Regional Cancer Center
  More Information

No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00723658     History of Changes
Other Study ID Numbers: CDR0000600963, S0629, U10CA032102
Study First Received: July 26, 2008
Last Updated: January 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
Waldenström macroglobulinemia

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases
Bortezomib
Cisplatin
Cyclophosphamide
Dexamethasone
Doxorubicin
Etoposide
Liposomal doxorubicin
Rituximab
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on October 23, 2014