Phase I Study for Safety and Efficacy of P276-00 in Subjects With Myeloma

A Phase 1 study testing P276-00 in people with Multiple Myeloma, run by Piramal Enterprises Limited.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial summary

This research study is a Phase I/II clinical trial. It is done to determine the best doses that the investigational drug (P276-00) can be used safely. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more information about it such as; the safest dose to use… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: P276-00
Type of treatment: Injection or infusion
How many people: 35 participants
Where: No sites listed yet
Study dates: Dec 2008to Jul 2010
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

1. Subject previously diagnosed with multiple myeloma based either on the standard or the International Myeloma Foundation (IMF) diagnostic criteria as defined in Appendix A 2. Subjects must have relapsed or relapsed/refractory disease after at least 2 prior lines of therapy as defined in Appendix D 3. Monoclonal protein in the serum of ³ 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of ³ 200 mg/ 24 hours, or measurable light chains by free light chain assay of ³ 10 mg/dL, or measurable plasmacytoma 4. Age ≥ 18 years at the time of signing the informed consent form 5. ECOG performance status < 2 6. Life expectancy > 3 months 7. Subjects must have the following laboratory parameters:
Hemoglobin > 8.0 gm/dL
Absolute neutrophil count (ANC) ≥1000 cells/mm3
Platelets count ≥ 50,000/mm3
Serum SGOT/AST <3.0 x institutional upper limits of normal (ULN)
Serum SGPT/ALT <3.0 x institutional upper limits of normal (ULN)
Serum creatinine <2.5mg/dL
Serum total bilirubin <1.5 x institutional upper limits of normal (ULN) 8. Woman of childbearing potential [defined as a sexually mature woman who has not undergone hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e. who has had menses any time in the preceding 24 consecutive months) with a negative serum pregnancy test. In addition, all sexually active woman of childbearing potential and men agreeing to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the duration of study participation and for at least 4 weeks after withdrawal from the study, unless they are surgically sterilised 9. Ability to understand and the willingness to sign a written informed consent document

Who cannot join

1. Subjects having received radiotherapy, immunotherapy, chemotherapy and or biological agents like G-CSF in the 2 weeks prior to day 1 of study drug administration and have not recovered completely from the side effects of the earlier investigational agent 2. Subjects having received any other investigational agents within 2 weeks prior to the date of enrolment 3. History of allergic reactions attributed to compounds of similar chemical composition to P276-00 4. Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months 5. Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or any other cancer for which the subject has been disease-free for at least 3 years 6. Subjects with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, known cardiac ejection fraction <40%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 7. Women who are pregnant or nursing 8. Subjects known to be seropositive for the human immunodeficiency virus 9. Subjects requiring the use of concomitant medications that prolong the QT/QTc interval and/or are known to cause Torsades de Pointes (TdP) 10. Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study

About this study

Official title: An Open Label, Multicenter Phase I Study To Evaluate Safety and Efficacy of P276-00 in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma

A majority of multiple myeloma patients overexpress a protein that plays a role in regulating the body's cell cycle called Cyclin D1. The study drug P276-00 is a Cyclin D1 inhibitor under investigation in the treatment of solid tumors. The researchers therefore believe that Cyclin D1 should be studied as a therapeutic target in myeloma. In this research study, we are looking for the highest dose of P276-00 that can be given safely and to see how well it works

Read the detailed description

The pre clinical data demonstrated that P276-00 is a selective Cdk4-D1 and Cdk1-B inhibitor with potent cytotoxic effects against MM cells including sensitive (MM1.S, RPMI 8226, OPM1, OPM2) and resistant (MM1.R, Dox-40, LR5) to conventional chemotherapy as well as in mouse xenograft models. The IC50 for this effect is between 300-1000 nM in vitro, and potential doses to be evaluated in the clinical study can achieve these concentrations. This evidence supports a rationale for evaluating the effects of P276-000 in patients with relapsed/refractory MM in order to determine safety and tolerability as well as pharmacokinetics and potential efficacy. The current study design allows for adequate assessment of patient safety in terms of the potential adverse effects of P276-00.

Conditions: Multiple Myeloma
Being tested: P276-00
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

P276-00Drug
IV drug infusion over a period of 30 min on day 1,4,8 and 11 in21 day cycle for 6 cycles

What is being measured

The primary outcome is the main question the study is designed to answer.

maximum tolerated dose (MTD) in subjects with relapsed and relapsed/refractory Multiple Myeloma (MM)
Measured: 1year

Secondary outcomes (1)

clinical response of P276-00 in subjects with relapsed and relapsed/refractory MM 2. Exploratory pharmacogenomic analysis of serum and molecular markers associated with P276-00 use in the study population
Measured: 1.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2008Jul 2010

First posted22 Oct 2007 (estimated)
Study startDec 2008
Primary completionDec 2009 (estimated)
Study completionJul 2010 (estimated)

Why it stopped: Not to expose the patients to subtherapeutic dose

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Multiple MyelomaStudies 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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00547404
Sponsor's protocol ID: P276-00/11/07
Status last verified: Apr 2009
First submitted: 19 Oct 2007
Last updated: 23 Apr 2009
Results posted: No
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Multicenter Phase I Study To Evaluate Safety and Efficacy of P276-00 in Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
ClinicalTrials.gov ID: NCT00547404
Acronym / sponsor ID: P276-00/11/07
Conditions: Multiple Myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Not to expose the patients to subtherapeutic dose
Enrolment: 35 participants (estimated)
Lead sponsor: Piramal Enterprises LimitedIndustry (pharma, biotech, devices)
Study start: Dec 2008
Primary completion: Dec 2009 (estimated)
Study completion: Jul 2010 (estimated)
First posted: 22 Oct 2007 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

1. Subject previously diagnosed with multiple myeloma based either on the standard or the International Myeloma Foundation (IMF) diagnostic criteria as defined in Appendix A 2. Subjects must have relapsed or relapsed/refractory disease after at least 2 prior lines of therapy as defined in Appendix D 3. Monoclonal protein in the serum of ³ 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of ³ 200 mg/ 24 hours, or measurable light chains by free light chain assay of ³ 10 mg/dL, or measurable plasmacytoma 4. Age ≥ 18 years at the time of signing the informed consent form 5. ECOG performance status < 2 6. Life expectancy > 3 months 7. Subjects must have the following laboratory parameters:

Key exclusion criteria (1 listed)

1. Subjects having received radiotherapy, immunotherapy, chemotherapy and or biological agents like G-CSF in the 2 weeks prior to day 1 of study drug administration and have not recovered completely from the side effects of the earlier investigational agent 2. Subjects having received any other investigational agents within 2 weeks prior to the date of enrolment 3. History of allergic reactions attributed to compounds of similar chemical composition to P276-00 4. Subjects with a history of myocardial infarction or uncontrolled cardiac dysfunction during the previous 6 months 5. Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or any other cancer for which the subject has been disease-free for at least 3 years 6. Subjects with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, known cardiac ejection fraction <40%, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 7. Women who are pregnant or nursing 8. Subjects known to be seropositive for the human immunodeficiency virus 9. Subjects requiring the use of concomitant medications that prolong the QT/QTc interval and/or are known to cause Torsades de Pointes (TdP) 10. Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study

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
P276-00IV drug infusion over a period of 30 min on day 1,4,8 and 11 in21 day cycle for 6 cycles	Drug	–

Primary outcome

maximum tolerated dose (MTD) in subjects with relapsed and relapsed/refractory Multiple Myeloma (MM)
Time frame: 1year

1 secondary outcome

clinical response of P276-00 in subjects with relapsed and relapsed/refractory MM 2. Exploratory pharmacogenomic analysis of serum and molecular markers associated with P276-00 use in the study population
Time frame: 1.5 years

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2009.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

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.

Noopur Raje, MD principal investigator

Dana-Farber Cancer Institute

Sagar Lonial, MD principal investigator

Winship Cancer Institute,Emory University

Sundar Jagannath, MD principal investigator

St. Vincent's Comprehensive Cancer Center

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing P276-00 in people with Multiple Myeloma, run by Piramal Enterprises Limited.

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 1 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: withdrawn, as of the sponsor's last update on 23 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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 (MTD) in subjects with relapsed and relapsed/refractory Multiple Myeloma (MM) (time frame: 1year). 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 NCT00547404.

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 23 Apr 2009.