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1 Clinical Trial Details (PDF Generation Date :- Wed, 28 Nov :04:58 GMT) CTRI Number CTRI/2009/091/ [Registered on: 28/10/2009] - Last Modified On 08/09/2014 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study Interventional Drug Single Arm Trial A phase II trial to study the efficacy and safety of a new drug P in the treatment of Mantle Cell Lymphoma Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) Details Contact Person (Scientific Query) Details Contact Person (Public Query) NCT P276-00/23/08 Affiliation ClinicalTrials.gov Protocol Number Details of Principal Investigator Details Contact Person (Scientific Query) Affiliation Senior Vice President, Clinical Research (R and D) Affiliation Details Contact Person (Public Query) page 1 / 5

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Details of Ethics Committee Source of Monetary or Material Support > Piramal Life Sciences Limited, 1, Nirlon Complex, Goregaon (E), - 63 Primary Sponsor Details Piramal Life Sciences Limited Nirlon Complex Off Western Express Highway Goregaon (East) , Type of Sponsor Pharmaceutical industry-n Piramal Life Sciences Limited 1, Nirlon Complex, Goregaon (E), - 63 List of Countries of Principal Investigator Dr. Anand Pathak Dr. Vinod Raina Dr. N. K. Warrier Dr. Kirushna Kumar Dr. Cecil Ross Dr Reena Nair of Site Site Phone/Fax/ Cancer Care Clinic and Hospital, 5th floor, Vasant Sheela Tower, Lokmat Square, Nagpur Institute Rotary Cancer Hospital, All Sciences, New Delhi Malabar Institute of Medical Sciences, Govindapuram, Calicut, Kerala- 16 Meenakshi mission hospital and research centre St. Johns Medical College & Hospital, Sarjapur Road, Bangalore 34 Tata Memorial Hospital, Dr. E. Borges Marg, Parel, Cancer Care Clinic and Hospital, 5th floor,,vasant Sheela Tower, Lokmat Square, Nagpur Institute Rotary Cancer Hospital,,All Sciences, New Delhi DELHI Malabar Institute of Medical Sciences,,Govi ndapuram-16 N/A Lake area, Melur road, Madurai TAMIL NADU St. Johns Medical College & Hospital,,Sarjapur Road, -34 Bangalore KARNATAKA Tata Memorial Hospital,,Dr. E. Borges Marg, Parel, jueely1194@yahoo.co.i n vinodraina@hotmail.co m n_goray@rediffmail.co m drkskk@yahoo.com cecilross@bsnl.in reenanair@ .com of Committee Approval Status Date of Approval Is Independent Ethics Committee? Central Medical Research Ethics page 2 / 5

3 Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Inclusion Criteria Exclusion Criteria Committee, Nagpur Ethical review board, meenakshi mission hospital and research centre, Madurai Human Ethics Committee, Tata Memorial Hospital Institute Ethics Committee, AIIMS Institutional Ethical Review Board Institutional Ethics Committee, Malabar Sciences, Calicut Status Approved 02/12/2009 Not Available Approved 18/01/2010 Not Available Date Approved/Obtained 20/07/2009 Health Type Patients Condition Mantle Cell Lymphoma Type Details Intervention P P will be administered to all patients at a dose of 185 mg/m2/day in 200 ml of 5% dextrose as an iv infusion over 30 minutes, on Days 1 to 5, every 21 days, for a minimum of 6 cycles and a maximum of 12 cycles. Comparator Agent Age From Age To Gender Details Details Not applicable; single arm study Not applicable Inclusion Criteria 1. Age >/=18 years 2. 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 3. Documented progression or relapse after at least 1 line of prior chemotherapy 4. Presence of measurable disease 5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 6. Life expectancy of at least 3 months 7. Ability to understand and the willingness to sign a written informed consent document (ICD) 8. Full recovery from all prior treatment toxicities to Common Terminology Criteria for Adverse Events (CTCAE) Grade </= 1 Exclusion Criteria 1. Prior radiation therapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration 2. 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. 3. Prior allogeneic stem cell transplantation within 1 year of study page 3 / 5

4 Method of Generating Random Sequence Method of Concealment Blinding/Masking Open Label drug administration 4. Current or prior CNS lymphoma 5. QTc 450 msec 6. Unstable angina, myocardial infarction, CHF or stroke within previous 6 months of study drug administration 7. Presence of active and serious comorbidity and uncontrolled illness other than MCL 8. 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 9. Hemoglobin 8.0 gm/dl 10. Absolute neutrophil count 1000/mm3 11. Platelet count 50,000/mm3 12. 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 Gilberts Disease) 13. Total bilirubin, 1.5 institutional ULN ( 3 institutional ULN if liver is involved with lymphoma or if patient has Gilberts Disease) 14. Serum creatinine 1.5 institutional ULN 15. Patients known to be suffering from infection with human immunodeficiency virus (HIV), tuberculosis, Hepatitis C or Hepatitis B 16. Pregnant or lactating women 17. Women of childbearing potential or men not willing to use at least 2 approved methods of contraception (1 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 Primary Outcome Outcome Timepoints Objective response rate End of every 2 cycles Secondary Outcome Outcome Timepoints Target Sample Size Phase of Trial Phase 2 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Duration of response Time to progression (TTP) Total Sample Size=25 Sample Size from =10 30/11/2009 No Date Specified Years=2 Months=6 Days=0 Other (Terminated) Other (Terminated) End of every 2 cycles 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) replapse. Prognosis of MCL after first relapse is very poor with median survival of around 1 to 2 years. Therefore novel page 4 / 5

5 Powered by TCPDF ( PDF of Trial therapies are required for relapsed and/or refractory MCL. Over-expression of Cyclin D1 as a result of t(11;14)(q13;q32) translocation is the hallmark of MCL. Therefore, inhibition of Cdk4-Cyclin D1 is a potentially promising target in MCL. P 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 P in the treatment of patients with relapsed and/or refractory MCL. This study is planned to be performed at multiple sites in the United States, Argentina and with the potential to be conducted in other countries that have not yet been finalized. Approximately five patients are proposed to be enrolled from. Anticipated date of first enrollment for the n arm is 30th November 2009 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 interim analysis following 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 P intravenous (iv) 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 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. Tumor measurements using spiral CT scan or MRI will be undertaken at screening and at the end of every 2 cycles. Response evaluation will be performed using the International Working Group (IWG) revised response criteria for malignant lymphoma. page 5 / 5