A Phase II Study to Evaluate Efficacy and Safety of P276-00 in Relapsed and/or Refractory Mantle Cell Lymphoma

This study has been terminated.
(The study was terminated based on interim results and all subjects were off study at that time. No major safety or tolerability concerns)
Sponsor:
Information provided by (Responsible Party):
Piramal Enterprises Limited
ClinicalTrials.gov Identifier:
NCT00843050
First received: February 12, 2009
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: P276-00
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Piramal Enterprises Limited:

Primary Outcome Measures:
  • Best Overall Objective Response Rate [ Time Frame: End of every 2 cycles and end of the study treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: End of the study treatment ] [ Designated as safety issue: No ]
    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.

  • Time to Progression [ Time Frame: End of study treatment ] [ Designated as safety issue: No ]
    It is defined as the time from day 1 of the study drug administration until the first date of progressive disease.


Enrollment: 13
Study Start Date: November 2009
Estimated Study Completion Date: August 2012
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00843050

Locations
United States, Arizona
Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona
Phoenix, Arizona, United States, 85054
Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona
Scottsdale, Arizona, United States, 85259
United States, Minnesota
College of Medicine, Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Ohio
Gabrail Cancer Center Research
Canton, Ohio, United States, 44718
Gabrail Cancer Center Research
Dover, Ohio, United States, 44622
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-5505
United States, Texas
Cancer Care Centers of South Texas
New Braunfels, Texas, United States, 78130
Cancer Care Centers of South Texas
San Antonio, Texas, United States, 78229
United States, Utah
Huntsman Cancer Institute, 2000 Circle of Hope, Room 2145
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Department of Medicine, University of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Dept of Hematology/Oncology, University of Wisconsin- Madison
Madison, Wisconsin, United States, 53792-5156
India
Institute Rotary Cancer Hospital, All India Institute of Medical Sciences
New Delhi, Delhi, India, 10029
St. Johns Medical College & Hospital
Bangalore, Karnataka, India, 34
Malabar Institute of Medical Sciences
Calicut, Kerala, India, 16
Jaslok Hospital and Research Centre
Mumbai, Maharashtra, India, 400 026
Tata Memorial Hospital
Mumbai, Maharashtra, India, 400012
Cancer Care Clinic and Hospital
Nagpur, Maharashtra, India, 440012
Meenakshi mission hospital and research centre
Madurai, Tamil nadu, India, 625107
Sponsors and Collaborators
Piramal Enterprises Limited
Investigators
Principal Investigator: Brad Kahl, MD Director of the Lymphoma Service and Associate Professor of Medicine, University of Wisconsin- Madison
Principal Investigator: Gabrail Nashat, MD CEO, President, Gabrail Cancer Center
Principal Investigator: Martha Glenn, MD Associate Professor of Medicine, Huntsman Cancer Institute, Salt Lake City
Principal Investigator: Andre Goy, MD Director of Lymphoma and Deputy Director of Cancer Center, Hackensack University Medical Center, Hackensack
Principal Investigator: Roger Lyons, MD President, Cancer Care Centers of South Texas , San Antonio
Principal Investigator: Nishitha Reddy, MD Vanderbilt University Medical Center, Nashville
Principal Investigator: Reena Nair, MD Professor and Medical Oncologist, Tata Memorial Hospital, Mumbai, India
Principal Investigator: Anand Pathak, MD Medical Oncologist, Cancer Care Clinic and Hospital, Nagpur, India
Principal Investigator: Vinod Raina, MD Head Dept of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
Principal Investigator: N K Warrier, MD Senior Consultant Oncologist, Malabar Institute of Medical Sciences, Calicut, India
Principal Investigator: Cecil Ross, MD Consultant Oncologist, St. Johns Medical College & Hospital, Bangalore, India
Principal Investigator: Kirushna kumar, MD Consultant Oncologist, Meenakshi mission hospital and research centre, Madurai, India
Principal Investigator: S H Advani, MD Consultant Oncologist, Jaslok Hospital and Research Centre, Mumbai, India
Principal Investigator: Patrick Johnston, MD Associate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, USA
Principal Investigator: Ajay Gopal, MD Associate Professor of Medicine, Department of Medicine, University of Washington, Seattle, Washington.
Principal Investigator: Craig Reeder, MD Consultant, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona
  More Information

No publications provided

Responsible Party: Piramal Enterprises Limited
ClinicalTrials.gov Identifier: NCT00843050     History of Changes
Other Study ID Numbers: P276-00/23/08
Study First Received: February 12, 2009
Results First Received: February 29, 2012
Last Updated: June 20, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
India: Drugs Controller General of India

Keywords provided by Piramal Enterprises Limited:
CKD inhibitor
Mantle Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 23, 2014