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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00843050
Other study ID # P276-00/23/08
Secondary ID
Status Terminated
Phase Phase 2
First received February 12, 2009
Last updated June 20, 2012
Start date November 2009
Est. completion date August 2012

Study information

Verified date June 2012
Source Piramal Enterprises Limited
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaIndia: Drugs Controller General of India
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 13
Est. completion date August 2012
Est. primary completion date February 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- 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

Study Design

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


Related Conditions & MeSH terms


Intervention

Drug:
P276-00
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

Locations

Country Name City State
India St. Johns Medical College & Hospital Bangalore Karnataka
India Malabar Institute of Medical Sciences Calicut Kerala
India Meenakshi mission hospital and research centre Madurai Tamil nadu
India Jaslok Hospital and Research Centre Mumbai Maharashtra
India Tata Memorial Hospital Mumbai Maharashtra
India Cancer Care Clinic and Hospital Nagpur Maharashtra
India Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi Delhi
United States Gabrail Cancer Center Research Canton Ohio
United States Gabrail Cancer Center Research Dover Ohio
United States Hackensack University Medical Center Hackensack New Jersey
United States Dept of Hematology/Oncology, University of Wisconsin- Madison Madison Wisconsin
United States Vanderbilt University Medical Center Nashville Tennessee
United States Cancer Care Centers of South Texas New Braunfels Texas
United States Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona Phoenix Arizona
United States College of Medicine, Mayo Clinic Rochester Minnesota
United States Huntsman Cancer Institute, 2000 Circle of Hope, Room 2145 Salt Lake City Utah
United States Cancer Care Centers of South Texas San Antonio Texas
United States Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona Scottsdale Arizona
United States Department of Medicine, University of Washington Seattle Washington
United States Seattle Cancer Care Alliance Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Piramal Enterprises Limited

Countries where clinical trial is conducted

United States,  India, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. End of every 2 cycles and end of the study treatment No
Secondary 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. End of the study treatment No
Secondary Time to Progression It is defined as the time from day 1 of the study drug administration until the first date of progressive disease. End of study treatment No
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