Phase 2 Study of VELCADE (Bortezomib) in Patients With Re... | NCT00715208

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
VELCADE R-CAP	Experimental	VELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 Intravenous on Day 1, cyclophosphamide 750 mg/m2 intravenous on Day 1, doxorubicin 50 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.	Drug: rituximab Drug: cyclophosphamide Drug: doxorubicin Drug: VELCADE Drug: prednisone
VELCADE R-CP	Experimental	VELCADE will be administered as a 3- to 5-second intravenous bolus injection, rituximab 375 mg/m2 intravenous on Day 1, cyclophosphamide 1000 mg/m2 intravenous on Day 1, VELCADE 1.6 mg/m2 intravenous on Days 1 and 8, prednisone 100 mg orally on Days 1 to 5 of a 21-day (3-week) cycle for 6 cycles.	Drug: rituximab Drug: cyclophosphamide Drug: VELCADE Drug: prednisone

Name	Type	Description	Arm Group Labels	Other Names
rituximab	Drug		VELCADE R-CAP VELCADE R-CP
cyclophosphamide

Measure	Description	Time Frame
Number of Patients With Complete Response (CR)	Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria.	30 weeks

Measure	Description	Time Frame
Number of Participants With Overall Response (OR)	OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria. CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET.	30 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female patient 18 years of age or older
Pathological diagnosis of follicular lymphoma (any grade) or marginal zone lymphoma. Patients with transformed follicular lymphoma are eligible, provided there has previously been pathologic documentation of follicular lymphoma.
Documented relapse or progression following prior antineoplastic therapy
At least 1 measurable tumor mass that is greater than 1.5 cm in the long axis and greater than 1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation
No clinically significant evidence of active central nervous system lymphoma
Karnofsky performance status (KPS) ≥50 (equivalent to Eastern Cooperative Group Oncology Group [ECOG] status ≤2)

Exclusion Criteria:

Diagnosed or treated for a malignancy other than Non-Hodgkin's Lymphoma (NHL) within 2 years of first dose, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Patients with prostate cancer who were treated with definitive radiotherapy who have a serum prostate-specific antigen <1 ng/mL are not excluded. Patients are not excluded if they have had basal cell or squamous cell carcinoma of the skin that was completely resected, or any in situ malignancy that was adequately treated.
Received any of the following treatments or procedures outside of the specified timeframes:
- Prior treatment with VELCADE
- Prior treatment with a cumulative dose of doxorubicin of more than 100 mg/m2, if assigned to Arm A (VELCADE-R-CAP)
- Antineoplastic (including unconjugated therapeutic antibodies and toxin immunoconjugates), experimental, or radiation therapy within 3 weeks before Day 1 of Cycle 1
- Nitrosoureas within 6 weeks before Day 1 of Cycle 1
- Radioimmunoconjugates within 10 weeks before Day 1 of Cycle 1
- Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time
- Major surgery within 2 weeks before Day 1 of Cycle 1

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Northwest Alabama Center, PC		Muscle Shoals	Alabama	35661	United States
Providence Saint Joseph Medical Center

PubMed Identifier	Type	Citation	Retractions
25039282	Derived	Craig M, Hanna WT, Cabanillas F, Chen CS, Esseltine DL, Neuwirth R, O'Connor OA. Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2014 Sep;166(6):920-8. doi: 10.1111/bjh.12991. Epub 2014 Jul 9.

Results Section

Participant Flow Module

ID	Title	Description
FG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
FG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With Complete Response (CR)

Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria.

Response evaluable: measurable disease at baseline, completed first scheduled response evaluation, or do not complete first scheduled response evaluation due to progressive disease (PD) or death.

Posted

Number

participants

30 weeks

ID	Title	Description
OG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
OG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Units	Counts
Participants	OG0006 OG00148

Title

Denominators

Categories

Title	Measurements
	OG0001(0 to 36) OG00113

Secondary

Number of Participants With Overall Response (OR)

OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria.

CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET.

Response evaluable: measurable disease at baseline, completed first scheduled response evaluation, or do not complete first scheduled response evaluation due to PD or death.

Posted

Number

participants

30 weeks

ID	Title	Description
OG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
OG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Progression-free Survival (PFS) at 1 Year

PFS was defined as the time from the first dose to the date of progressive disease (PD)/relapse or death, whichever comes first. For a participant who had not progressed/relapsed or died, PFS was censored at the last response assessment that was stable disease (failure to attain complete response/partial response or PD or better).

Safety population: Treated

Posted

Number

percentage of participants

Assessed at at the end of Cycle 2, at end of treatment visit, and every 12± 1 weeks for the first year (4 visits) until PD

ID	Title	Description
OG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
OG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Units	Counts
Participants	OG000

Secondary

Duration of Response

Time (in months) from the first documentation of a response (CR or partial response [PR]) to the date of first documentation of progressive disease or relapse from complete response.

CR is defined as disappearance of all evidence of disease assessed by CT or PET; PR is defined as regression of measurable disease and no new sites assessed by CT or PET according to the revised International Working Group (IWG) Criteria.

Responders: CR + PR (Not done for VELCADE R-CAP, only 5 responders)

Posted

Median

95% Confidence Interval

Months

2 years

ID	Title	Description
OG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
OG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Units	Counts
Participants	OG000

Secondary

Number of Patients Who Experienced at Least One Serious Adverse Event

Safety Population: Treated patients

Posted

Number

participants

From completion of informed consent through 30 days after the last dose of study drug

ID	Title	Description
OG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
OG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Statistical Information
Bronchitis NOS	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Bronchitis acute NOS	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Pneumonia NOS	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Bacteraemia	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Neutropenic sepsis	Infections and infestations	EG0001 affected7 at risk EG0010 affected48 at risk
Oropharyngeal candidiasis	Infections and infestations	EG0001 affected7 at risk EG0010 affected48 at risk
Respiratory tract infection NOS	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Cellulitis	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Viral infection NOS	Infections and infestations	EG0000 affected7 at risk EG0011 affected48 at risk
Pyrexia	General disorders	EG0001 affected7 at risk EG0013 affected48 at risk
Fatigue	General disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Weakness	General disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Febrile neutropenia	Blood and lymphatic system disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Neutropenia	Blood and lymphatic system disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Lymphadenopathy	Blood and lymphatic system disorders	EG0000 affected7 at risk EG0012 affected48 at risk
Leukopenia NOS	Blood and lymphatic system disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Dyspnoea NOS	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Chronic obstructive airways disease exacerbated	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Lung infiltration NOS	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Respiratory failure (excl neonatal)	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Cardiac failure congestive	Cardiac disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Myocardial infarction	Cardiac disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Atrial fibrillation	Cardiac disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Ascites	Gastrointestinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Abdominal pain NOS	Gastrointestinal disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Blood culture positive	Investigations	EG0000 affected7 at risk EG0012 affected48 at risk
Electrocardiogram T wave abnormal	Investigations	EG0000 affected7 at risk EG0011 affected48 at risk
Back pain	Musculoskeletal and connective tissue disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Pain in limb	Musculoskeletal and connective tissue disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Syncope	Nervous system disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Headache NOS	Nervous system disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Vision blurred	Eye disorders	EG0000 affected7 at risk EG0011 affected48 at risk
Hypertension aggravated	Vascular disorders	EG0000 affected7 at risk EG0011 affected48 at risk

Other Adverse Events

Term	Organ System	Statistical Information
Diarrhoea	Gastrointestinal disorders	EG0002 affected7 at risk EG00124 affected48 at risk
Nausea	Gastrointestinal disorders	EG0003 affected7 at risk EG00121 affected48 at risk
Vomiting NOS	Gastrointestinal disorders	EG0000 affected7 at risk EG00112 affected48 at risk
Constipation	Gastrointestinal disorders	EG0003 affected7 at risk EG00110 affected48 at risk
Stomatitis	Gastrointestinal disorders	EG0003 affected7 at risk EG0012 affected48 at risk
Pharyngolaryngeal pain	Gastrointestinal disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Alopecia	Skin and subcutaneous tissue disorders	EG0004 affected7 at risk EG0018 affected48 at risk
Night sweats	Skin and subcutaneous tissue disorders	EG0002 affected7 at risk EG0012 affected48 at risk
Dry skin	Skin and subcutaneous tissue disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Skin lesion NOS	Skin and subcutaneous tissue disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Skin hypopigmentation	Skin and subcutaneous tissue disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Nail disorder	Skin and subcutaneous tissue disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Rigors	General disorders	EG0004 affected7 at risk EG0016 affected48 at risk
Oedema lower limb	General disorders	EG0002 affected7 at risk EG0015 affected48 at risk
Fatigue aggravated	General disorders	EG0001 affected7 at risk EG0015 affected48 at risk
Infusion associated symptoms	General disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Fall	General disorders	EG0002 affected7 at risk EG0010 affected48 at risk
Chest pain	General disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Anorexia	Metabolism and nutrition disorders	EG0002 affected7 at risk EG0016 affected48 at risk
Dehydration	Metabolism and nutrition disorders	EG0003 affected7 at risk EG0013 affected48 at risk
Hypocalcaemia	Metabolism and nutrition disorders	EG0002 affected7 at risk EG0012 affected48 at risk
Hyperglycaemia NOS	Metabolism and nutrition disorders	EG0001 affected7 at risk EG0013 affected48 at risk
Hypokalaemia	Metabolism and nutrition disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Hyponatraemia	Metabolism and nutrition disorders	EG0001 affected7 at risk EG0012 affected48 at risk
Hyperuricaemia	Metabolism and nutrition disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Anaemia	Blood and lymphatic system disorders	EG0003 affected7 at risk EG0018 affected48 at risk
Thrombocytopenia	Blood and lymphatic system disorders	EG0003 affected7 at risk EG0016 affected48 at risk
Lymphopenia	Blood and lymphatic system disorders	EG0002 affected7 at risk EG0016 affected48 at risk
Peripheral neuropathy NOS	Nervous system disorders	EG0002 affected7 at risk EG00110 affected48 at risk
Peripheral sensory neuropathy	Nervous system disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Peripheral neuropathy aggravated	Nervous system disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Dizziness (excl vertigo)	Nervous system disorders	EG0002 affected7 at risk EG0017 affected48 at risk
Dysgeusia	Nervous system disorders	EG0004 affected7 at risk EG0011 affected48 at risk
Paraesthesia	Nervous system disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Restless leg syndrome	Nervous system disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Upper respiratory tract infection NOS	Infections and infestations	EG0000 affected7 at risk EG0018 affected48 at risk
Herpes zoster	Infections and infestations	EG0001 affected7 at risk EG0013 affected48 at risk
Urinary tract infection NOS	Infections and infestations	EG0001 affected7 at risk EG0013 affected48 at risk
Nasopharyngitis	Infections and infestations	EG0001 affected7 at risk EG0011 affected48 at risk
Cough	Respiratory, thoracic and mediastinal disorders	EG0001 affected7 at risk EG0018 affected48 at risk
Rhinitis NOS	Respiratory, thoracic and mediastinal disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	EG0002 affected7 at risk EG0010 affected48 at risk
Pulmonary congestion	Respiratory, thoracic and mediastinal disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	EG0000 affected7 at risk EG0016 affected48 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	EG0001 affected7 at risk EG0015 affected48 at risk
Bone pain	Musculoskeletal and connective tissue disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Myalgia	Musculoskeletal and connective tissue disorders	EG0001 affected7 at risk EG0012 affected48 at risk
Muscle cramps	Musculoskeletal and connective tissue disorders	EG0002 affected7 at risk EG0011 affected48 at risk
Peripheral swelling	Musculoskeletal and connective tissue disorders	EG0000 affected7 at risk EG0013 affected48 at risk
White blood cell count decreased	Investigations	EG0001 affected7 at risk EG0014 affected48 at risk
Lymphocyte count decreased	Investigations	EG0000 affected7 at risk EG0014 affected48 at risk
Neutrophil count decreased	Investigations	EG0000 affected7 at risk EG0014 affected48 at risk
Haemoglobin decreased	Investigations	EG0000 affected7 at risk EG0016 affected48 at risk
Blood uric acid increased	Investigations	EG0000 affected7 at risk EG0014 affected48 at risk
Platelet count decreased	Investigations	EG0000 affected7 at risk EG0014 affected48 at risk
Blood glucose increased	Investigations	EG0000 affected7 at risk EG0013 affected48 at risk
Blood urea increased	Investigations	EG0001 affected7 at risk EG0011 affected48 at risk
Blood creatinine increased	Investigations	EG0001 affected7 at risk EG0010 affected48 at risk
Insomnia	Psychiatric disorders	EG0002 affected7 at risk EG0017 affected48 at risk
Confusion	Psychiatric disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Hypotension NOS	Vascular disorders	EG0002 affected7 at risk EG0012 affected48 at risk
Flushing	Vascular disorders	EG0000 affected7 at risk EG0013 affected48 at risk
Lacrimation increased	Eye disorders	EG0000 affected7 at risk EG0014 affected48 at risk
Eye irritation	Eye disorders	EG0000 affected7 at risk EG0014 affected48 at risk
Tachycardia NOS	Cardiac disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Sinus Tachycardia	Cardiac disorders	EG0001 affected7 at risk EG0012 affected48 at risk
Ventricular hypokinesia	Cardiac disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Renal failure acute	Renal and urinary disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Tinnitus	Ear and labyrinth disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Hypoproteinaemia	Hepatobiliary disorders	EG0001 affected7 at risk EG0011 affected48 at risk
Hypersensitivity NOS	Immune system disorders	EG0001 affected7 at risk EG0010 affected48 at risk
Breast discomfort	Reproductive system and breast disorders	EG0001 affected7 at risk EG0010 affected48 at risk

Ancestor Terms

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D001897	Boronic Acids
D000148	Acids, Noncarboxylic
D000143	Acids
D007287	Inorganic Chemicals
D001896	Boron Compounds
D011719	Pyrazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds

ID	Term
D008228	Lymphoma, Non-Hodgkin
D008223	Lymphoma
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D000069283	Rituximab
D003520	Cyclophosphamide
D004317	Doxorubicin
D000069286	Bortezomib
D011241	Prednisone

ID	Title	Description
BG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin
BG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	VELCADE R-CAP	VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin			2	7	7	7
EG001	VELCADE R-CP	VELCADE, rituximab, cyclophosphamide, and prednisone			12	48	47	48