NCT00295932 · REGISTRY CONDITION SEARCH

Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2018-11-20

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with cyclophosphamide, prednisone, and rituximab may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of bortezomib when given together with cyclophosphamide, prednisone, and rituximab and to see how well it works in treating patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Maximum Tolerated Dose

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Duration of Response (Mean and Median)

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outcome · POSTED

Event-free Survival

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outcome · POSTED

Overall Survival

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outcome · POSTED

Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Chronic lymphocytic leukemia (CLL) * B-cell small lymphocytic leukemia (SLL) * Any marginal zone lymphoma * Grade 1-3A follicular lymphoma * Waldenstrom's macroglobulinemia * Mantle cell lymphoma * No transformed indolent lymphoma * Assessable disease (phase I) * Measurable disease (phase I and II), defined as ≥ one lesion that can be accurately measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT scan * Lymph nodes measuring ≤ 1 cm in the short axis are considered normal * Relapsed or refractory disease * Must have received at least 1 prior therapeutic regimen but no more than 3 prior conventional cytotoxic therapy regimens * No known brain metastases or meningeal disease PATIENT CHARACTERISTICS: * Karnofsky performance status \> 50% * Absolute neutrophil count \> 1,000/mcl (more than 500/mcl if known lymphomatous involvement) * Platelet count ≥ 50,000/mcl * Total bilirubin \< 1.5 times upper limit of normal (ULN) (less than 5 mg/dL if known history of Gilbert's disease) * AST and ALT ≤ 2.5 times ULN (4 times ULN if liver involvement) * Creatinine \< 1.5 times ULN OR creatinine clearance \> 50 mL/min * Patients may have febrile episodes up to 38.5ºC without evidence of active infection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No New York Heart Association class III or IV congestive heart failure * No uncontrolled intercurrent illness, including any of the following: * Ongoing or active infection * Cerebrovascular accident or transient ischemic attack within 6 months of study entry * Unstable angina pectoris * Cardiac arrhythmia * EKG evidence of acute ischemia * Psychiatric illness/social situations that would limit compliance with study requirements * No uncontrolled hypertension requiring active manipulation of antihypertensive medications * No known or active HIV infection * No history of hypersensitivity to bortezomib, boron, or mannitol * No peripheral neuropathy \> grade 2 * No other malignancy within the past 5 years except curatively treated non life-threatening malignancies, such as cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * Prior stem cell transplantation allowed * Preparative cytoreductive and high-dose therapies considered 1 prior therapy * At least 4 weeks since prior cytotoxic chemotherapy (6 weeks since prior nitrosoureas or mitomycin C) * At least 12 weeks since prior radioimmunotherapy * One prior course comprising tositumomab or ibritumomab tiuxetan allowed * At least 1 week since prior palliative steroids for NHL * No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab, alemtuzumab, etc.) within 3 months of study entry * Patients treated with monoclonal antibodies within 3 months allowed provided disease progressed on this therapy AND no treatment received 7 days prior to study entry * Seven days since prior rituximab (for patients enrolled in phase I portion) * No major surgery within 4 weeks of study entry * No other concurrent investigational agents * No other concurrent anticancer therapy
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
intervention Names
Biological: rituximab
Drug: bortezomib
Drug: cyclophosphamide
Drug: prednisone
label
Arm I
type
EXPERIMENTAL
description
Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
intervention Names
Biological: rituximab
Drug: bortezomib
Drug: cyclophosphamide
Drug: prednisone
label
Arm II
type
EXPERIMENTAL

interventions

arm Group Labels
Arm I
Arm II
description
Given IV
name
rituximab
type
BIOLOGICAL
arm Group Labels
Arm I
Arm II
description
Given IV
name
bortezomib
type
DRUG
arm Group Labels
Arm I
Arm II
description
Given IV
name
cyclophosphamide
type
DRUG
arm Group Labels
Arm I
Arm II
description
Given orally
name
prednisone
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 79
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Maximum tolerated dose of Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone in Phase I participants
measure
Maximum Tolerated Dose
time Frame
2 years

secondary Outcomes

measure
Progression-free Survival
time Frame
2 years
measure
Duration of Response (Mean and Median)
time Frame
2 years
measure
Event-free Survival
time Frame
2 years
measure
Overall Survival
time Frame
2 years
description
Toxicity assessed using NCI-CTC v. 3.0
measure
Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma
time Frame
2 years

Full study description

brief Summary: RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with cyclophosphamide, prednisone, and rituximab may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of bortezomib when given together with cyclophosphamide, prednisone, and rituximab and to see how well it works in treating patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma.
detailed Description: OBJECTIVES: Primary * Determine the maximum tolerated dose of bortezomib when given in combination with rituximab, cyclophosphamide, and prednisone (R-CP) in patients with relapsed or refractory indolent B-cell lymphoproliferative disorders or mantle cell lymphoma. (phase I) * Determine the frequency and duration of complete and partial responses in patients treated with two different treatment regimes. (phase II) Secondary * Evaluate the progression-free survival, event-free survival, and overall survival of patients treated with this regimen. (phase II) * Evaluate the toxicity profile of this regimen. OUTLINE: This is a phase I dose-escalation study of bortezomib followed by a phase II randomized, multicenter study. Patients in phase II are stratified according to disease (mantle cell lymphoma vs indolent B-cell lymphoproliferative disorder vs transformed lymphoma). * Phase I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV on days 2 and 7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 1 month, every 4 months for 2 years, and then every 6 months thereafter.

Source references

references

citation
Gerecitano J, Portlock C, Hamlin P, Moskowitz CH, Noy A, Straus D, Schulman P, Dumitrescu O, Sarasohn D, Pappanicholaou J, Iasonos A, Zhang Z, Mo Q, Horanlli E, Rojas CN, Zelenetz AD, O'Connor OA. Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-Hodgkin lymphoma. Clin Cancer Res. 2011 Apr 15;17(8):2493-501. doi: 10.1158/1078-0432.CCR-10-1498. Epub 2011 Feb 23.
pmid
21346146
type
RESULT