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

NCT ID: NCT00843050

Last Updated: 2012-07-27

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2012-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Mantle Cell Lymphoma

Keywords

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CKD inhibitor Mantle Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

P276-00

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Piramal Enterprises Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brad Kahl, MD

Role: PRINCIPAL_INVESTIGATOR

Director of the Lymphoma Service and Associate Professor of Medicine, University of Wisconsin- Madison

Gabrail Nashat, MD

Role: PRINCIPAL_INVESTIGATOR

CEO, President, Gabrail Cancer Center

Martha Glenn, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine, Huntsman Cancer Institute, Salt Lake City

Andre Goy, MD

Role: PRINCIPAL_INVESTIGATOR

Director of Lymphoma and Deputy Director of Cancer Center, Hackensack University Medical Center, Hackensack

Roger Lyons, MD

Role: PRINCIPAL_INVESTIGATOR

President, Cancer Care Centers of South Texas , San Antonio

Nishitha Reddy, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center, Nashville

Reena Nair, MD

Role: PRINCIPAL_INVESTIGATOR

Professor and Medical Oncologist, Tata Memorial Hospital, Mumbai, India

Anand Pathak, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncologist, Cancer Care Clinic and Hospital, Nagpur, India

Vinod Raina, MD

Role: PRINCIPAL_INVESTIGATOR

Head Dept of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

N K Warrier, MD

Role: PRINCIPAL_INVESTIGATOR

Senior Consultant Oncologist, Malabar Institute of Medical Sciences, Calicut, India

Cecil Ross, MD

Role: PRINCIPAL_INVESTIGATOR

Consultant Oncologist, St. Johns Medical College & Hospital, Bangalore, India

Kirushna kumar, MD

Role: PRINCIPAL_INVESTIGATOR

Consultant Oncologist, Meenakshi mission hospital and research centre, Madurai, India

S H Advani, MD

Role: PRINCIPAL_INVESTIGATOR

Consultant Oncologist, Jaslok Hospital and Research Centre, Mumbai, India

Patrick Johnston, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine, College of Medicine, Mayo Clinic, Rochester, USA

Ajay Gopal, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine, Department of Medicine, University of Washington, Seattle, Washington.

Craig Reeder, MD

Role: PRINCIPAL_INVESTIGATOR

Consultant, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona

Locations

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Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, Arizona

Phoenix, Arizona, United States

Site Status

Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Arizona

Scottsdale, Arizona, United States

Site Status

College of Medicine, Mayo Clinic

Rochester, Minnesota, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status

Gabrail Cancer Center Research

Dover, Ohio, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Cancer Care Centers of South Texas

New Braunfels, Texas, United States

Site Status

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Site Status

Huntsman Cancer Institute, 2000 Circle of Hope, Room 2145

Salt Lake City, Utah, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Department of Medicine, University of Washington

Seattle, Washington, United States

Site Status

Dept of Hematology/Oncology, University of Wisconsin- Madison

Madison, Wisconsin, United States

Site Status

St. Johns Medical College & Hospital

Bangalore, Karnataka, India

Site Status

Malabar Institute of Medical Sciences

Calicut, Kerala, India

Site Status

Jaslok Hospital and Research Centre

Mumbai, Maharashtra, India

Site Status

Tata Memorial Hospital

Mumbai, Maharashtra, India

Site Status

Cancer Care Clinic and Hospital

Nagpur, Maharashtra, India

Site Status

Institute Rotary Cancer Hospital, All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Site Status

Meenakshi mission hospital and research centre

Madurai, Tamil Nadu, India

Site Status

Countries

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Argentina United States India

Other Identifiers

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P276-00/23/08

Identifier Type: -

Identifier Source: org_study_id