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

NCT00723658 | Withdrawn Phase 2 DMC

• 2 other identifiers: S0629U10CA032102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 29

Brief 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.

Conditions

Lymphoma

Keywords

Waldenström macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 3 years

  3 years

Secondary Outcomes (4)

• Overall survival

  3 years

• Response rate (complete response, very good partial response, and partial response)

  3 years

• Standard prognostic factors and other potential correlates that may relate to progression, symptomatic disease, and/or survival

  3 years

• Toxicity

  3 years

Study Arms (2)

Observation

NO INTERVENTION

Non-symptomatic patients are monitored monthly for 3 months, then every 3 months thereafter.

Treatment

EXPERIMENTAL

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

Interventions

rituximab BIOLOGICAL

Treatment

bortezomib DRUG

Treatment

carmustine DRUG

Treatment

cisplatin DRUG

Treatment

cyclophosphamide DRUG

Treatment

cytarabine DRUG

Treatment

dexamethasone DRUG

Treatment

doxorubicin hydrochloride DRUG

Treatment

etoposide DRUG

Treatment

melphalan DRUG

Treatment

thalidomide DRUG

Treatment

autologous-autologous tandem hematopoietic stem cell transplantation PROCEDURE

Treatment

peripheral blood stem cell transplantation PROCEDURE

Treatment

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

Study Sites (29)

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, 06105, United States

Location

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, 46107, United States

Location

Reid Hospital & Health Care Services

Richmond, Indiana, 47374, United States

Location

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

Location

Wesley Medical Center

Wichita, Kansas, 67214, United States

Location

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, 48106-0995, United States

Location

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, 48106, United States

Location

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, 48123-2500, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Foote Memorial Hospital

Jackson, Michigan, 49201, United States

Location

Sparrow Regional Cancer Center

Lansing, Michigan, 48912-1811, United States

Location

St. Mary Mercy Hospital

Livonia, Michigan, 48154, United States

Location

St. Joseph Mercy Oakland

Pontiac, Michigan, 48341-2985, United States

Location

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, 48060, United States

Location

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, 48601, United States

Location

St. John Macomb Hospital

Warren, Michigan, 48093, United States

Location

Grandview Hospital

Dayton, Ohio, 45405, United States

Location

Good Samaritan Hospital

Dayton, Ohio, 45406, United States

Location

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

CCOP - Dayton

Dayton, Ohio, 45420, United States

Location

Blanchard Valley Medical Associates

Findlay, Ohio, 45840, United States

Location

Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

Location

Charles F. Kettering Memorial Hospital

Kettering, Ohio, 45429, United States

Location

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, 45373-1300, United States

Location

Clinton Memorial Hospital

Wilmington, Ohio, 45177, United States

Location

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, 45385, United States

Location

MeSH Terms

Conditions

Lymphoma; Waldenstrom Macroglobulinemia

Interventions

Rituximab; Bortezomib; Carmustine; Cisplatin; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Melphalan; Thalidomide; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Gordan Srkalovic, MD, PhD

  Sparrow Regional Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 26, 2008
• First Posted: July 29, 2008
• Study Start: September 1, 2008
• Primary Completion: May 1, 2010
• Last Updated: March 6, 2015

Record last verified: 2015-03

Locations

US (29)