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

Phase 1
18 Years
Not Enrolling
Multiple Myeloma

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Trial Information

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

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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:


Safety Issue:


Principal Investigator

Noopur Raje, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

December 2008

Completion Date:

July 2010

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell