LeukemiaPhase 1/2NCT00295932
Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
A Phase 1/2 study testing rituximab, bortezomib and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- rituximab, bortezomib and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 8 sitesUnited States
- Study dates
- 13 Dec 2005to 11 Mar 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08903
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Memorial Sloan-Kettering at Mercy Medical Center
Rockville Centre, New York
Memoral Sloan Kettering Cancer Center@Phelps
Sleepy Hollow, New York
About this study
Official title: A Phase II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)
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.
Read the 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.
- Being tested
- rituximab, bortezomib, cyclophosphamide, prednisone
- Keywords
- recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, Waldenstrom macroglobulinemia, recurrent mantle cell lymphoma, refractory chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Given IV
bortezomibDrug
Given IV
cyclophosphamideDrug
Given IV
prednisoneDrug
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | 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. Receives: Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone |
| Arm II | Experimental | 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. Receives: Biological: rituximab; Drug: bortezomib; Drug: cyclophosphamide; Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Maximum tolerated dose of Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone in Phase I participants
Measured: 2 years
Secondary outcomes (5)
Progression-free Survival
Measured: 2 years
Duration of Response (Mean and Median)
Measured: 2 years
Event-free Survival
Measured: 2 years
Overall Survival
Measured: 2 years
Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma
Toxicity assessed using NCI-CTC v. 3.0
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2006 (estimated)
- Study start13 Dec 2005
- Primary completion11 Mar 2018
- Study completion11 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey, Columbia University, Emory University
- Responsible party
- Sponsor
- Investigators
- Carol Portlock, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00295932
- Sponsor's protocol ID
- 05-103
- Other IDs
- MSKCC-05103
- Status last verified
- Mar 2018
- First submitted
- 23 Feb 2006
- Last updated
- 20 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 21346146
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)
- ClinicalTrials.gov ID
- NCT00295932
- Acronym / sponsor ID
- 05-103
- Keywords
- recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent small lymphocytic lymphoma, recurrent marginal zone lymphoma, Waldenstrom macroglobulinemia, recurrent mantle cell lymphoma, refractory chronic lymphocytic leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Rutgers Cancer Institute of New Jersey, Columbia University, Emory University
- Study start
- 13 Dec 2005 (actual)
- Primary completion
- 11 Mar 2018 (actual)
- Study completion
- 11 Mar 2018 (actual)
- First posted
- 24 Feb 2006 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: rituximab, Drug: bortezomib, Drug: cyclophosphamide, Drug: prednisonePatients 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 | Experimental | Biological: rituximab, Drug: bortezomib, Drug: cyclophosphamide, Drug: prednisonePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabGiven IV | Biological | Arm I, Arm II |
| bortezomibGiven IV | Drug | Arm I, Arm II |
| cyclophosphamideGiven IV | Drug | Arm I, Arm II |
| prednisoneGiven orally | Drug | Arm I, Arm II |
Primary outcome
Maximum Tolerated Dose
Time frame: 2 years
Maximum tolerated dose of Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone in Phase I participants
5 secondary outcomes
Progression-free Survival
Time frame: 2 years
Duration of Response (Mean and Median)
Time frame: 2 years
Event-free Survival
Time frame: 2 years
Overall Survival
Time frame: 2 years
Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21346146Gerecitano 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.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol Portlock, MD principal investigator
Memorial Sloan Kettering Cancer Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rituximab, bortezomib and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00295932, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2018.