Mantle Cell LymphomaPhase 1NCT01439750
Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)
A Phase 1 study testing Rituximab, bortezomib and Cladribine in people with Mantle Cell Lymphoma, run by Milton S. Hershey Medical Center at 2 sites in United States.
Trial summary
This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma
- What is being tested?
- Rituximab, bortezomib and Cladribine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2012to Aug 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Females that are postmenopausal for at least 1 year before the screening visit, surgically sterilized or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose.
- Male subjects must agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Patients with newly diagnosed and relapsed mantle cell lymphoma.
- ECOG performance status grade 3 or higher.
Who cannot join
- Patient has a platelet count of <50x10 9/L within 14 days before enrollment if not related to disease.
- Patient has an absolute neutrophil count less than 100 within 14 days before enrollment if not related to disease.
- Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
- Patient has > 1.5 x ULN total bilirubin.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class II or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
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- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding.
- Patient has received other investigational drugs within 14 days before enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma: A Phase I/II Study (PSHCI 10-011)
This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated for the incidence of dose-liming toxicity (DLT) at each dose level. Once the maximum tolerated dose (MTD) is determined, a phase II component with 2 arms will begin. One arm will enroll newly diagnosed MCL patients and one arm will enroll relapsed MCL patients. Each arm is a single-stage, fixed sample size study and will be accrued and analyzed separately. The phase I and II data will also be analyzed separately.
Read the detailed description
The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Three patients are enrolled on a dose level. If 0 out of 3 patients have DLT, then the next set of 3 patients are enrolled at the next highest dose level. If ≥2 out of 3 patients have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be enrolled at the next lowest dose level if only 3 were treated previously at that level. If 1 out of 3 patients have DLT, then the next set of 3 patients will be treated at the same dose level. If ≤1 out of 6 patients treated at that dose level have DLT, then the next set of patients will be treated at the next higher dose level. If ≥2 out of 6 patients treated at that dose level have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be treated at the next lowest dose level if only 3 were treated previously at that level. This phase I study will use 3 dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2), with 3 mg/m2 being the starting dose level. DLTs will be assessed at the completion of the first 2 cycles of cladribine and rituximab.
Phase II Design: The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms.
Due to difficulties with enrollment, this trial will not move into the intended Phase II of the proposed Phase I/II study. This study will only be Phase I.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- Rituximab, bortezomib, Cladribine
- Keywords
- mantle cell lymphoma, lymphoma
- Medical subject headings
- Lymphoma, Mantle-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxam
375 mg/m2 on day 5, 12, 19, 26 of Cycle1; and day 5 of Cycles 2-6; then every 2 months as maintenenace dose
bortezomibDrug
Also called VELCADE
1.6 mg/m2 day 12, 19, 26 for 3 cycles (28 days). Then beginning with Cycle 4, 1.6/mg/m2 every two weeks (Days 5 and 19; maintenance every other week until toxicity or proression of disease).
CladribineDrug
Also called Litak, Movectro
Phase I will use 3 dose levels Level 1: caldribine (2-CdA) 3mg/m2 days 1-5; Level 2 caldribine 4mg/m2 days 1-5; Level 3: cladribine 5mg/m2 days 1-5
| Study group | Role | What they receive |
|---|---|---|
| Phase I | Experimental | The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of cladribine in the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Rituximab 375 mg/m2 on day 5,12, 19, 26 for 1st cycle, then day 5 of cladribine for next 5 cycles and then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days 1-5 for 6 cycles. Bortezomib 1.6 mg/m2 sub Q days 12,19,26 for 3 cycle, then every 2 weeks maintenance dose until toxicity or progression. Receives: Drug: Rituximab; Drug: bortezomib; Drug: Cladribine |
| Phase II | Experimental | The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms. Rituximab 375 mg/m2 on day 5,12,19,26 for 1st cycles, then day 5 montly for next 5 cycles, then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days for 6 cycles (dose determined from phase I). Bortezomib 1.6 mg/m2 weekly on day 12,19,26 for 3 cycles then every 2 weeks as maintenance dose until toxicity or progression. Receives: Drug: Rituximab; Drug: bortezomib; Drug: Cladribine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome Dose Limiting Tolerability
Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .
Measured: 2 years
Secondary outcomes (1)
Secondary Outcome objective response rates
Estimate objective response rates of the VCR regimen in B cell malignancies where response to therapy is assessed per the revised Cheson criteria (2007) and the overall survival of patients treated with this combination for the Phase 2 portion of the study.
Measured: 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2011 (estimated)
- Study startMay 2012
- Primary completionAug 2018 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey J. Pu, MD, PhD, Milton S. Hershey Medical Center
- Investigators
- Jeffrey J Pu, MD PhD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01439750
- Sponsor's protocol ID
- PSHCI 10-011
- Status last verified
- Aug 2017
- First submitted
- 16 Aug 2011
- Last updated
- 7 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: May share data
Publications
Pu JJ, Berger KN, Zheng C, Do N, Claxton DF, Ehmann WC, Drabick JJ, Li H, Loughran TP Jr, Epner EM. A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma. Front Oncol. 2024 Dec 16;14:1449401. doi: 10.3389/fonc.2024.1449401. eCollection 2024.
PubMed 39737396
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma: A Phase I/II Study (PSHCI 10-011)
- ClinicalTrials.gov ID
- NCT01439750
- Acronym / sponsor ID
- PSHCI 10-011
- Conditions
- Mantle Cell Lymphoma
- Keywords
- mantle cell lymphoma, lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- May 2012 (actual)
- Primary completion
- Aug 2018 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 23 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated for the incidence of dose-liming toxicity (DLT) at each dose level. Once the maximum tolerated dose (MTD) is determined, a phase II component with 2 arms will begin. One arm will enroll newly diagnosed MCL patients and one arm will enroll relapsed MCL patients. Each arm is a single-stage, fixed sample size study and will be accrued and analyzed separately. The phase I and II data will also be analyzed separately.
Detailed description
The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Three patients are enrolled on a dose level. If 0 out of 3 patients have DLT, then the next set of 3 patients are enrolled at the next highest dose level. If ≥2 out of 3 patients have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be enrolled at the next lowest dose level if only 3 were treated previously at that level. If 1 out of 3 patients have DLT, then the next set of 3 patients will be treated at the same dose level. If ≤1 out of 6 patients treated at that dose level have DLT, then the next set of patients will be treated at the next higher dose level. If ≥2 out of 6 patients treated at that dose level have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be treated at the next lowest dose level if only 3 were treated previously at that level. This phase I study will use 3 dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2), with 3 mg/m2 being the starting dose level. DLTs will be assessed at the completion of the first 2 cycles of cladribine and rituximab.
Phase II Design: The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms.
Due to difficulties with enrollment, this trial will not move into the intended Phase II of the proposed Phase I/II study. This study will only be Phase I.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase I | Experimental | Drug: Rituximab, Drug: bortezomib, Drug: CladribineThe phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of cladribine in the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Rituximab 375 mg/m2 on day 5,12, 19, 26 for 1st cycle, then day 5 of cladribine for next 5 cycles and then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days 1-5 for 6 cycles. Bortezomib 1.6 mg/m2 sub Q days 12,19,26 for 3 cycle, then every 2 weeks maintenance dose until toxicity or progression. |
| Phase II | Experimental | Drug: Rituximab, Drug: bortezomib, Drug: CladribineThe phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms. Rituximab 375 mg/m2 on day 5,12,19,26 for 1st cycles, then day 5 montly for next 5 cycles, then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days for 6 cycles (dose determined from phase I). Bortezomib 1.6 mg/m2 weekly on day 12,19,26 for 3 cycles then every 2 weeks as maintenance dose until toxicity or progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Females that are postmenopausal for at least 1 year before the screening visit, surgically sterilized or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose.
- Male subjects must agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Patients with newly diagnosed and relapsed mantle cell lymphoma.
- ECOG performance status grade 3 or higher.
Key exclusion criteria (11 listed)
- Patient has a platelet count of <50x10 9/L within 14 days before enrollment if not related to disease.
- Patient has an absolute neutrophil count less than 100 within 14 days before enrollment if not related to disease.
- Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
- Patient has > 1.5 x ULN total bilirubin.
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: Rituxam375 mg/m2 on day 5, 12, 19, 26 of Cycle1; and day 5 of Cycles 2-6; then every 2 months as maintenenace dose | Drug | Phase I, Phase II |
| bortezomibAlso: VELCADE1.6 mg/m2 day 12, 19, 26 for 3 cycles (28 days). Then beginning with Cycle 4, 1.6/mg/m2 every two weeks (Days 5 and 19; maintenance every other week until toxicity or proression of disease). | Drug | Phase I, Phase II |
| CladribineAlso: Litak, MovectroPhase I will use 3 dose levels Level 1: caldribine (2-CdA) 3mg/m2 days 1-5; Level 2 caldribine 4mg/m2 days 1-5; Level 3: cladribine 5mg/m2 days 1-5 | Drug | Phase I, Phase II |
Primary outcome
Primary Outcome Dose Limiting Tolerability
Time frame: 2 years
Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .
1 secondary outcome
Secondary Outcome objective response rates
Time frame: 7 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2017.
- Derived from this study: PubMed 39737396Pu JJ, Berger KN, Zheng C, Do N, Claxton DF, Ehmann WC, Drabick JJ, Li H, Loughran TP Jr, Epner EM. A phase I study using bortezomib (Velcade), cladribine, and rituximab in treating patients over 50 years old with mantle cell lymphoma. Front Oncol. 2024 Dec 16;14:1449401. doi: 10.3389/fonc.2024.1449401. eCollection 2024.
- Individual participant dataSharing planned: Undecided. May share data
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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.
Jeffrey J Pu, MD PhD principal investigator
Milton S. Hershey 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 study testing Rituximab, bortezomib and Cladribine in people with Mantle Cell Lymphoma, run by Milton S. Hershey 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 4 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 7 Aug 2017. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Primary Outcome Dose Limiting Tolerability (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 NCT01439750, 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 7 Aug 2017.