Trial record 1 of 1 for:    NCT02004522
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A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02004522
First received: November 13, 2013
Last updated: July 11, 2016
Last verified: July 2016
  Purpose
A Phase 3 clinical trial to examine the efficacy of IPI-145 monotherapy versus ofatumumab monotherapy in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Condition Intervention Phase
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: IPI-145 (duvelisib)
Drug: Ofatumumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (DUO)

Resource links provided by NLM:


Further study details as provided by Infinity Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: Until disease progression or unacceptable toxicity assessed up to 6 years ] [ Designated as safety issue: No ]
  • Hematologic improvements [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Every 6 months for up to 3 years after first dose ] [ Designated as safety issue: No ]
  • Lymph node response rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Lymph node response defined as greater than or equal to 50% decrease in the SPD of target lymph nodes

  • Duration of Response (DOR) [ Time Frame: Time from the first documentation of response to first documentation of progressive disease or death due to any cause ] [ Designated as safety issue: No ]
  • Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values [ Time Frame: 30 days plus 7 days from last dose ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) [ Time Frame: Cycle 2, Cycle 3, and Cycle 7 ] [ Designated as safety issue: No ]
    Evaluate the PK of IPI-145 and, if applicable, its metabolite(s)


Estimated Enrollment: 300
Study Start Date: November 2013
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPI-145
IPI-145 is administered orally and supplied as 5 mg and 25 mg formulated capsules
Drug: IPI-145 (duvelisib)
Other Name: PI3K Inhibitor
Active Comparator: Ofatumumab
Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5mL and 1000 mg/50 mL
Drug: Ofatumumab
Other Name: Arzerra

Detailed Description:

This is an open-label, two- arm, randomized phase 3, superiority trial designed to evaluate the efficacy and safety of IPI-145 compared to ofatumumab administered to patients who have been diagnosed with CLL/SLL whose disease is relapsed or refractory.

Approximately 150 subjects will receive a starting dose of 25 mg IPI-145 BID initially over the course of 21-day treatment cycle followed by 28-day treatment cycles for up to 18 cycles.

Approximately 150 subjects will receive a starting dose of 300 mg ofatumumab on Day 1 followed by seven weekly doses of 2000 mg. Thereafter, subjects will receive 2000 mg ofatumumab once every month for four months. Administration of ofatumumab will not exceed the 12 doses (within 7 cycles).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ≥ B and/or Rai Stage ≥ I)
  • Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy
  • Not appropriate for treatment with a purine-based analogue regimen (per National Comprehensive Cancer Network [NCCN] or European Society for Medical Oncology [ESMO] guidelines), including relapse ≤ 36 months from a purine-based chemoimmunotherapy regimen or relapse ≤ 24 months from a purine-based monotherapy regimen
  • A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification
  • Measurable disease with a lymph node or tumor mass > 1.5 cm in at least one dimension as assessed by computed tomography (CT)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] ≥ 60%)
  • Willingness by subject to be randomized to receive either ofatumumab or duvelisib at the dose and schedule defined in the protocol
  • Must meet the following laboratory parameters:

    1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN)
    2. Total bilirubin ≤ 1.5 x ULN
    3. Serum creatinine ≤ 2.0 x ULN
    4. Hemoglobin ≥ 8.0 g/dL with or without transfusion support
    5. Platelet count ≥ 10,000 μL with or without transfusion support
  • For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women ≤ 55 years] or 12 consecutive months [women > 55 years])
  • Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
  • Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
  • Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed

Exclusion Criteria:

  • History of Richter's transformation or prolymphocytic leukemia
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requiring > 20 mg once daily (QD) of prednisone (or equivalent) to maintain hemoglobin > 8.0 g/dL or platelets > 10,000 μL without transfusion support
  • Refractory to ofatumumab (progression or relapse <12 months of receiving ofatumumab therapy or <24 months of receiving an ofatumumab- containing regimen)
  • Prior allogeneic transplant (prior autologous stem cell transplant >6 months prior to study entry is permitted)
  • Known central nervous system lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization
  • Use of any of the following medications or procedures within the specified timeframe:

    • Use of live or live attenuated vaccines within 30 days prior to randomization
    • Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization
    • Tyrosine kinase inhibitor within 7 days of randomization
    • Other investigational therapy (not included above) within 3 weeks of randomization
  • Previous treatment with a PI3K inhibitor or BTK inhibitor
  • Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD
  • History of tuberculosis treatment within the preceding two years
  • Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring IV antimicrobial, antifungal or antiviral agents)

    − Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at randomization

  • Human immunodeficiency virus (HIV) infection
  • Prior, current, or chronic hepatitis B or hepatitis C infection
  • History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
  • Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)
  • Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) Note: This criterion does not apply to subjects with a right or left bundle branch block (BBB)
  • Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk while participating in this study
  • Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease free for ≥2 years
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
  • Administration of medications or foods that are strong inhibitors or inducers of CYP3A within 2 weeks of randomization
  • Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
  • Major surgery or invasive intervention within 4 weeks prior to randomization
  • Pregnant or breastfeeding women
  • Hypersensitivity to ofatumumab or its excipients
  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: NCT02004522

  Show 92 Study Locations
Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
Investigators
Study Director: Virginia Kelly, MD Infinity Pharmaceuticals, Inc.
  More Information

Responsible Party: Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02004522     History of Changes
Other Study ID Numbers: IPI-145-07 
Study First Received: November 13, 2013
Last Updated: July 11, 2016
Health Authority: Austria: Federal Office for Safety in Health Care
Austria: Agency for Health and Food Safety
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Italy: The Italian Medicines Agency
New Zealand: Medsafe
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Infinity Pharmaceuticals, Inc.:
Phase 3
CLL/SLL
Pi3K

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 22, 2016