Mantle Cell LymphomaPhase 2NCT00843050
A Phase II Study to Evaluate Efficacy and Safety of P276-00 in Relapsed and/or Refractory Mantle Cell Lymphoma
A Phase 2 study testing P276-00 in people with Mantle Cell Lymphoma, run by Piramal Enterprises Limited at 20 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether P276-00 is safe and effective in treatment of Mantle Cell Lymphoma that is recurred after or not responding to at least one previous line of treatment. 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?
- P276-00
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 20 sitesin 2 countries
- Study dates
- Nov 2009to Aug 2012
- Phase
- Phase 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
- Age ≥18 years
- Histological diagnosis of MCL and presence of either nuclear Cyclin D1 positivity by immunohistochemistry or t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping
- Documented progression or relapse after at least 1 line of prior chemotherapy
- Presence of measurable disease
- ECOG performance status 0, 1, or 2
- Life expectancy of at least 3 months
- Ability to understand and the willingness to sign a written informed consent document (ICD)
- Full recovery from all prior treatment toxicities of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1
Who cannot join
- Prior radiation therapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration
- Prior treatment with monoclonal antibodies or any radio- or toxin- immunoconjugates within 3 months of study drug administration; however, a patient who has had rituximab treatment within 3 months and has had PD after such treatment is allowed in the study.
- Prior allogeneic stem cell transplantation within 1 year of study drug administration
- Current or prior CNS lymphoma
- QTc > 450 msec
- Unstable angina, myocardial infarction, CHF or stroke within previous 6 months of study drug administration
Show all 17Show fewer
- Presence of active and serious comorbidity and uncontrolled illness other than MCL
- History of other prior malignancies except for properly treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer or early stage prostate cancer
- Hemoglobin <8.0 gm/dL
- Absolute neutrophil count <1000/mm3
- Platelet count <50,000/mm3
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 × institutional upper limit of normal (ULN) (> 5 × institutional ULN if liver is involved with lymphoma or if patient has Gilbert's Disease)
- Total bilirubin, >1.5 × institutional ULN (> 3 × institutional ULN if liver is involved with lymphoma or if patient has Gilbert's Disease)
- Serum creatinine >1.5 × institutional ULN
- Patients known to be suffering from infection with human immunodeficiency virus (HIV), tuberculosis, Hepatitis C or Hepatitis B
- Pregnant or lactating women
- Women of childbearing potential or men not willing to use at least 2 approved methods of contraception (one of which being a barrier method) after signing the ICD, during the entire study and for at least 4 weeks following withdrawal from the study
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States13 sites
Gabrail Cancer Center Research
Canton, Ohio, 44718
Gabrail Cancer Center Research
Dover, Ohio, 44622
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Dept of Hematology/Oncology, University of Wisconsin- Madison
Madison, Wisconsin, 53792-5156
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-5505
Cancer Care Centers of South Texas
New Braunfels, Texas, 78130
Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona
Phoenix, Arizona, 85054
College of Medicine, Mayo Clinic
Rochester, Minnesota, 55905
Huntsman Cancer Institute, 2000 Circle of Hope, Room 2145
Salt Lake City, Utah, 84112
Cancer Care Centers of South Texas
San Antonio, Texas, 78229
Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona
Scottsdale, Arizona, 85259
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Department of Medicine, University of Washington
Seattle, Washington, 98195
India7 sites
St. Johns Medical College & Hospital
Bangalore, Karnataka, 34
Malabar Institute of Medical Sciences
Calicut, Kerala, 16
Meenakshi mission hospital and research centre
Madurai, Tamil Nadu, 625107
Jaslok Hospital and Research Centre
Mumbai, Maharashtra, 400 026
Tata Memorial Hospital
Mumbai, Maharashtra, 400012
Cancer Care Clinic and Hospital
Nagpur, Maharashtra, 440012
Institute Rotary Cancer Hospital, All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 10029
About this study
Official title: Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P276-00 in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma
The purpose of this study is to determine whether P276-00 is safe and effective in treatment of Mantle Cell Lymphoma that is recurred after or not responding to at least one previous line of treatment.
Read the detailed description
Despite response rates of up to 97% with first-line standard or high-intensity chemotherapy, with or without stem-cell transplantation, most patients of mantle cell lymphoma (MCL)relapse.Prognosis of MCL after first relapse is very poor with median survival of around 1 to 2 years. Therefore, novel therapies are required for relapsed and/or refractory MCL.Overexpression of Cyclin D1 as a result of t(11;14)(q13;q32) translocation is the hallmark of MCL.It is postulated that Cyclin D1 may also have an oncogenic role independent of pRb in MCL.Therefore, inhibition of Cdk4-Cyclin D1 is a potentially promising target in MCL. P276-00 is a potent Cdk4-Cyclin D1 inhibitor worth exploring for its efficacy in MCL. Hence, this Phase II study is planned to examine the efficacy and safety of P276-00 in the treatment of patients with relapsed and/or refractory MCL.
This is an open-label, single-arm, 2-stage trial. Approximately 35 patients are planned to be enrolled into the study to obtain a total of 25 efficacy evaluable patients (patients who complete at least 2 cycles of study treatment and have tumor measurements at the end of 2 cycles). A total of 15 efficacy evaluable patients are planned to be treated in Stage I of the study. If ≥1 response (CR or PR) of any duration or ≥2 stable disease (SD) for ≥4 cycles are seen in the Stage I, then the study will continue into Stage II, in which additional patients will be treated until there are 10 additional efficacy evaluable patients.The study is divided into 3 periods: Screening, Treatment, and Follow-up. During the Screening Period, patients will provide written informed consent and be evaluated for inclusion and exclusion criteria. During the Treatment Period, patients will be administered P276-00 as intravenous (iv) infusion on Days 1 to 5 of each 21-day cycle for a minimum of 6 cycles and a maximum of 12 cycles, or until progressive disease (PD) or unacceptable toxicity occurs. Safety and efficacy evaluations will be done on Days 1 to 5 and 11 of each cycle, and on Day 21 of every 2 cycles. Pharmacokinetic (PK) assessments will be done on Cycle 1, Day 1 (pre-dose and post-dose time points), and optional biomarker assessments will be done pre-dose within 4 weeks of Day 1 and post-dose on Day 4 or 5. The End-of-Last-Cycle Visit will occur at the end of Cycle 6, or if the patient continues study treatment beyond Cycle 6, it will occur at the end of the patient's last cycle; if the patient discontinues early, these assessments will be done as an Early Exit Visit. The Follow-up Visit will occur 4 weeks (±1 week) after the End-of-Last-Cycle Visit (or Early Exit Visit) for final safety assessments.Objective response rate is the primary end point for this study. Response evaluation will be performed using the International Working Group (IWG) revised response criteria for malignant lymphoma.
- Conditions
- Mantle Cell Lymphoma
- Being tested
- P276-00
- Keywords
- CKD inhibitor, Mantle Cell Lymphoma
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P276-00Drug
P276-00: All patients will receive P276-00 185 mg/m2/day as intravenous infusion over 30 minutes in 200 ml of 5% dextrose from day 1 to day 5 in each 21 days cycle for minimum 6 and maximum 12 cycles or until there is progression of disease or unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| P276-00 | Experimental | P276-00: All patients will receive P276-00 185 mg/m2/day as intravenous infusion over 30 minutes in 200 ml of 5% dextrose from day 1 to day 5 in each 21 days cycle for minimum 6 and maximum 12 cycles or until there is progression of disease or unacceptable toxicity Receives: Drug: P276-00 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Objective Response Rate
The primary efficacy endpoint is the proportion of subjects achieving an objective response. The proportion of patients achieving an objective response is the best overall objective response rate.
Measured: End of every 2 cycles and end of the study treatment
Secondary outcomes (2)
Duration of Response
It is defined as the time from when the measurement criteria are met for complete or partial response until the first date that recurrent or progressive disease is objectively or clinically documented.
Measured: End of the study treatment
Time to Progression
It is defined as the time from day 1 of the study drug administration until the first date of progressive disease.
Measured: End of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2009 (estimated)
- Study startNov 2009
- Primary completionFeb 2011
- Study completionAug 2012 (estimated)
Why it stopped: The study was terminated based on interim results and all subjects were off study at that time. No major safety or tolerability concerns
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 Mantle Cell LymphomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Piramal Enterprises Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Brad Kahl, MD, Principal investigator, Director of the Lymphoma Service and Associate Professor of Medicine, University of Wisconsin- MadisonGabrail Nashat, MD, Principal investigator, CEO, President, Gabrail Cancer CenterMartha Glenn, MD, Principal investigator, Associate Professor of Medicine, Huntsman Cancer Institute, Salt Lake CityAndre Goy, MD, Principal investigator, Director of Lymphoma and Deputy Director of Cancer Center, Hackensack University Medical Center, HackensackRoger Lyons, MD, Principal investigator, President, Cancer Care Centers of South Texas , San AntonioNishitha Reddy, MD, Principal investigator, Vanderbilt University Medical Center, NashvilleReena Nair, MD, Principal investigator, Professor and Medical Oncologist, Tata Memorial Hospital, Mumbai, IndiaAnand Pathak, MD, Principal investigator, Medical Oncologist, Cancer Care Clinic and Hospital, Nagpur, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00843050
- Sponsor's protocol ID
- P276-00/23/08
- Status last verified
- Jun 2012
- First submitted
- 12 Feb 2009
- Last updated
- 27 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P276-00 in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00843050
- Acronym / sponsor ID
- P276-00/23/08
- Conditions
- Mantle Cell Lymphoma
- Keywords
- CKD inhibitor, Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated based on interim results and all subjects were off study at that time. No major safety or tolerability concerns
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Piramal Enterprises LimitedIndustry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Feb 2011 (actual)
- Study completion
- Aug 2012 (estimated)
- First posted
- 13 Feb 2009 (estimated)
- Results
- Posted 27 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether P276-00 is safe and effective in treatment of Mantle Cell Lymphoma that is recurred after or not responding to at least one previous line of treatment.
Detailed description
Despite response rates of up to 97% with first-line standard or high-intensity chemotherapy, with or without stem-cell transplantation, most patients of mantle cell lymphoma (MCL)relapse.Prognosis of MCL after first relapse is very poor with median survival of around 1 to 2 years. Therefore, novel therapies are required for relapsed and/or refractory MCL.Overexpression of Cyclin D1 as a result of t(11;14)(q13;q32) translocation is the hallmark of MCL.It is postulated that Cyclin D1 may also have an oncogenic role independent of pRb in MCL.Therefore, inhibition of Cdk4-Cyclin D1 is a potentially promising target in MCL. P276-00 is a potent Cdk4-Cyclin D1 inhibitor worth exploring for its efficacy in MCL. Hence, this Phase II study is planned to examine the efficacy and safety of P276-00 in the treatment of patients with relapsed and/or refractory MCL.
This is an open-label, single-arm, 2-stage trial. Approximately 35 patients are planned to be enrolled into the study to obtain a total of 25 efficacy evaluable patients (patients who complete at least 2 cycles of study treatment and have tumor measurements at the end of 2 cycles). A total of 15 efficacy evaluable patients are planned to be treated in Stage I of the study. If ≥1 response (CR or PR) of any duration or ≥2 stable disease (SD) for ≥4 cycles are seen in the Stage I, then the study will continue into Stage II, in which additional patients will be treated until there are 10 additional efficacy evaluable patients.The study is divided into 3 periods: Screening, Treatment, and Follow-up. During the Screening Period, patients will provide written informed consent and be evaluated for inclusion and exclusion criteria. During the Treatment Period, patients will be administered P276-00 as intravenous (iv) infusion on Days 1 to 5 of each 21-day cycle for a minimum of 6 cycles and a maximum of 12 cycles, or until progressive disease (PD) or unacceptable toxicity occurs. Safety and efficacy evaluations will be done on Days 1 to 5 and 11 of each cycle, and on Day 21 of every 2 cycles. Pharmacokinetic (PK) assessments will be done on Cycle 1, Day 1 (pre-dose and post-dose time points), and optional biomarker assessments will be done pre-dose within 4 weeks of Day 1 and post-dose on Day 4 or 5. The End-of-Last-Cycle Visit will occur at the end of Cycle 6, or if the patient continues study treatment beyond Cycle 6, it will occur at the end of the patient's last cycle; if the patient discontinues early, these assessments will be done as an Early Exit Visit. The Follow-up Visit will occur 4 weeks (±1 week) after the End-of-Last-Cycle Visit (or Early Exit Visit) for final safety assessments.Objective response rate is the primary end point for this study. Response evaluation will be performed using the International Working Group (IWG) revised response criteria for malignant lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| P276-00 | Experimental | Drug: P276-00P276-00: All patients will receive P276-00 185 mg/m2/day as intravenous infusion over 30 minutes in 200 ml of 5% dextrose from day 1 to day 5 in each 21 days cycle for minimum 6 and maximum 12 cycles or until there is progression of disease 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 (8 listed)
- Age ≥18 years
- Histological diagnosis of MCL and presence of either nuclear Cyclin D1 positivity by immunohistochemistry or t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping
- Documented progression or relapse after at least 1 line of prior chemotherapy
- Presence of measurable disease
- ECOG performance status 0, 1, or 2
Key exclusion criteria (17 listed)
- Prior radiation therapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration
- Prior treatment with monoclonal antibodies or any radio- or toxin- immunoconjugates within 3 months of study drug administration; however, a patient who has had rituximab treatment within 3 months and has had PD after such treatment is allowed in the study.
- Prior allogeneic stem cell transplantation within 1 year of study drug administration
- Current or prior CNS lymphoma
- QTc > 450 msec
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 |
|---|---|---|
| P276-00P276-00: All patients will receive P276-00 185 mg/m2/day as intravenous infusion over 30 minutes in 200 ml of 5% dextrose from day 1 to day 5 in each 21 days cycle for minimum 6 and maximum 12 cycles or until there is progression of disease or unacceptable toxicity | Drug | P276-00 |
Primary outcome
Best Overall Objective Response Rate
Time frame: End of every 2 cycles and end of the study treatment
The primary efficacy endpoint is the proportion of subjects achieving an objective response. The proportion of patients achieving an objective response is the best overall objective response rate.
2 secondary outcomes
Duration of Response
Time frame: End of the study treatment
Time to Progression
Time frame: End of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2012.
- 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.
Brad Kahl, MD principal investigator
Director of the Lymphoma Service and Associate Professor of Medicine, University of Wisconsin- Madison
Gabrail Nashat, MD principal investigator
CEO, President, Gabrail Cancer Center
Martha Glenn, MD principal investigator
Associate Professor of Medicine, Huntsman Cancer Institute, Salt Lake City
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing P276-00 in people with Mantle Cell Lymphoma, run by Piramal Enterprises Limited at 20 sites in 2 countries.
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 8 inclusion and 17 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: stopped early, as of the sponsor's last update on 27 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, India. 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 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 27 Jul 2012). 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?
Best Overall Objective Response Rate (time frame: End of every 2 cycles and end of the study treatment). 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 27 Jul 2012.