LymphomaPhase 1/2NCT00863369
Bortezomib and Gemcitabine in Treating Patients With Relapsed B-Cell Non-Hodgkin Lymphoma
A Phase 1/2 study testing rituximab, bortezomib and gemcitabine hydrochloride in people with Lymphoma, run by City of Hope Medical Center at 2 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 gemcitabine hydrochloride, 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
- Conditions the study is for
- Lymphoma
- What is being tested?
- rituximab, bortezomib and gemcitabine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Jun 2005to 20 Jun 2023
- 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
Who may be able to join
- Patients must have histologically or cytologically confirmed intermediate or high grade B-cell Non-Hodgkin lymphoma with primary progressive or relapsed disease
- Patients may have had up to 4 prior chemo-and-or radiation therapy regiments, including one autologous transplant based protocol; any prior therapy (chemotherapy or radiation) must have been completed at least 4 weeks prior to start of this protocol; for prior high-dose chemotherapy with stem cell transplant, a 6-week interval is required; all side effects must have resolved
- Karnofsky performance status >= 60%
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1,500 mm^3
- Platelets >= 50,000 mm^3
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- Total bilirubin =< 1.5 mg/dl
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min for creatinine levels above institutional normal (calculated or measured)
- Cardiac ejection fraction of > 40% by echocardiogram or multi gated acquisition (MUGA) scan
- Have no serious or intercurrent medical illness
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- Male subject agrees to use an acceptable method for contraception for the duration of the study
Who cannot join
- Patient has a platelet count of < 20 x 10^9/L with 7 days before enrollment
- Patient has an absolute neutrophil count of < 1.0 x 10^9/L within 7 days before enrollment
- Patient has a calculated or measured creatinine clearance of < 30 ml/min with 14 days before enrollment
- Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment
- Patient has hypersensitivity to bortezomib, boron, or mannitol
- Female subject is pregnant or breastfeeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women
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- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Patients who have had more than 4 prior different chemotherapy regimens will be excluded; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for autologous transplant regimens) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not have previously received VELCADE or gemcitabine
- Patients with active central nervous system (CNS) involvement are not eligible
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope Medical Center
Duarte, California, 91010-3000
South Pasadena Cancer Center
South Pasadena, California, 91030
About this study
Official title: A Phase I/II Study of VELCADE in Combination With Gemcitabine in Relapsed B-Cell Non-Hodgkin's Lymphoma
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 gemcitabine hydrochloride, 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 gemcitabine hydrochloride and rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib and gemcitabine hydrochloride when given together with rituximab and to see how well they work in treating patients with progressive or relapsed B-cell non-Hodgkin lymphoma.
Read the detailed description
OBJECTIVES:
Primary:
- To evaluate the safety and feasibility of combining VELCADE (bortezomib) with gemcitabine (gemcitabine hydrochloride) in patients with recurrent lymphoma after standard therapy.
II. To define the maximum tolerated dose (MTD) of gemcitabine and Rituxan (rituximab) administered in combination with VELCADE given on a 21-day (old schema - Schema I) or 28-day (amended schema - Schema II) schedule.
Secondary:
- To obtain preliminary data for response to this regimen in this patient population.
OUTLINE: This is a phase I, dose-escalation study of bortezomib and gemcitabine hydrochloride followed by a phase II study.
Patients receive bortezomib intravenously (IV), gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
- Conditions
- Lymphoma
- Being tested
- rituximab, bortezomib, gemcitabine hydrochloride, questionnaire administration
- Keywords
- recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, adult grade III lymphomatoid granulomatosis
- Medical subject headings
- Lymphoma, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
questionnaire administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib, gemcitabine hydrochloride, rituximab) | Experimental | Patients receive bortezomib IV, gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: bortezomib; Drug: gemcitabine hydrochloride; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With at Least One Dose Limiting Toxicity (DLT)
Adverse events were graded by NCI CTCAE, Version 3.0. DLT defined as grade 4 thrombocytopenia, or grade 3 thrombocytopenia lasting greater than 7 days. Grade 4 neutropenia lasting 7 days or more despite use of growth factors. Febrile neutropenia only is it occurs after 7 days of neutropenia. Any grade 3 or higher non-hematologic toxicity related to the study drug, with the exception of alopecia, inadequately treated nausea, vomiting and/or diarrhea and fatigue.
Measured: 28 days from start of treatment, up to 2 years.
Recommended Phase II Dose
The maximum tolerated dose (MTD) of Gemcitabine in combination with 1.3 mg/m2 of velcade on days 1 and 15 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
Measured: 28 days from start of treatment, up to 2 years.
Secondary outcomes (1)
Number of Subject With Complete Response
Per standard lymphoma response criteria (Cheson): Complete Response (CR), 1. Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy, with normalization of LDH if elevated prior to therapy. 2. All lymph nodes and masses must regress to normal size (<1.5 cm in greatest transverse diameter if >1.5 cm prior to treatment). 3. The spleen, if enlarged prior to therapy, must have regressed to normal size. 3. If bone marrow was involved by lymphoma, it must be cleared as documented by biopsy at the same location.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2009 (estimated)
- Study start29 Jun 2005
- Primary completion25 Aug 2016
- Study completion20 Jun 2023
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.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Leslie Popplewell, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00863369
- Sponsor's protocol ID
- 04115
- Other IDs
- P30CA033572, CHNMC-04115, MILLENNIUM-CHNMC-04115, CDR0000637492, NCI-2010-00925
- Status last verified
- Mar 2023
- First submitted
- 17 Mar 2009
- Last updated
- 20 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of VELCADE in Combination With Gemcitabine in Relapsed B-Cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00863369
- Acronym / sponsor ID
- 04115
- Conditions
- Lymphoma
- Keywords
- recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 3 follicular lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 29 Jun 2005 (actual)
- Primary completion
- 25 Aug 2016 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 18 Mar 2009 (estimated)
- Results
- Posted 21 Mar 2023
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 gemcitabine hydrochloride, 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 gemcitabine hydrochloride and rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib and gemcitabine hydrochloride when given together with rituximab and to see how well they work in treating patients with progressive or relapsed B-cell non-Hodgkin lymphoma.
Detailed description
OBJECTIVES:
Primary:
- To evaluate the safety and feasibility of combining VELCADE (bortezomib) with gemcitabine (gemcitabine hydrochloride) in patients with recurrent lymphoma after standard therapy.
II. To define the maximum tolerated dose (MTD) of gemcitabine and Rituxan (rituximab) administered in combination with VELCADE given on a 21-day (old schema - Schema I) or 28-day (amended schema - Schema II) schedule.
Secondary:
- To obtain preliminary data for response to this regimen in this patient population.
OUTLINE: This is a phase I, dose-escalation study of bortezomib and gemcitabine hydrochloride followed by a phase II study.
Patients receive bortezomib intravenously (IV), gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bortezomib, gemcitabine hydrochloride, rituximab) | Experimental | Biological: rituximab, Drug: bortezomib, Drug: gemcitabine hydrochloride, Other: questionnaire administrationPatients receive bortezomib IV, gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 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
Key inclusion criteria (14 listed)
- Patients must have histologically or cytologically confirmed intermediate or high grade B-cell Non-Hodgkin lymphoma with primary progressive or relapsed disease
- Patients may have had up to 4 prior chemo-and-or radiation therapy regiments, including one autologous transplant based protocol; any prior therapy (chemotherapy or radiation) must have been completed at least 4 weeks prior to start of this protocol; for prior high-dose chemotherapy with stem cell transplant, a 6-week interval is required; all side effects must have resolved
- Karnofsky performance status >= 60%
- Life expectancy of greater than 3 months
- Absolute neutrophil count >= 1,500 mm^3
Key exclusion criteria (13 listed)
- Patient has a platelet count of < 20 x 10^9/L with 7 days before enrollment
- Patient has an absolute neutrophil count of < 1.0 x 10^9/L within 7 days before enrollment
- Patient has a calculated or measured creatinine clearance of < 30 ml/min with 14 days before enrollment
- Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment
- Patient has hypersensitivity to bortezomib, boron, or mannitol
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 |
|---|---|---|
| rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV | Biological | Treatment (bortezomib, gemcitabine hydrochloride, rituximab) |
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (bortezomib, gemcitabine hydrochloride, rituximab) |
| gemcitabine hydrochlorideAlso: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarGiven IV | Drug | Treatment (bortezomib, gemcitabine hydrochloride, rituximab) |
| questionnaire administrationAncillary studies | Other | Treatment (bortezomib, gemcitabine hydrochloride, rituximab) |
Primary outcome
Number of Participants With at Least One Dose Limiting Toxicity (DLT)
Time frame: 28 days from start of treatment, up to 2 years.
Adverse events were graded by NCI CTCAE, Version 3.0. DLT defined as grade 4 thrombocytopenia, or grade 3 thrombocytopenia lasting greater than 7 days. Grade 4 neutropenia lasting 7 days or more despite use of growth factors. Febrile neutropenia only is it occurs after 7 days of neutropenia. Any grade 3 or higher non-hematologic toxicity related to the study drug, with the exception of alopecia, inadequately treated nausea, vomiting and/or diarrhea and fatigue.
Recommended Phase II Dose
Time frame: 28 days from start of treatment, up to 2 years.
The maximum tolerated dose (MTD) of Gemcitabine in combination with 1.3 mg/m2 of velcade on days 1 and 15 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
1 secondary outcome
Number of Subject With Complete Response
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Leslie Popplewell, MD principal investigator
City of Hope Medical Center
2 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 gemcitabine hydrochloride in people with Lymphoma, run by City of Hope Medical Center at 2 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?
The sponsor lists 14 inclusion and 13 exclusion criteria. 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 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 21 Mar 2023). 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?
Number of Participants With at Least One Dose Limiting Toxicity (DLT) (time frame: 28 days from start of treatment, up to 2 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Mar 2024.