Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies

NCT01871675 | Completed Phase 1

• 1 other identifier: SCRI HEMREF 34
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this study is to characterize the safety, maximum tolerated dose (MTD) and preliminary efficacy profile of IPI-145 given in combination with rituximab, or bendamustine plus rituximab, to subjects with select relapsed/refractory hematologic malignancies.

Conditions

Lymphoma; Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; T-cell Lymphoma

Keywords

Lymphoma; Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; T-cell Lymphoma; Rituxan; Bendamustine; Hematologic Malignancy; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• The number of adverse events, serious adverse events, and dose limiting toxicities as a measure of safety and tolerability

  The maximum tolerated dose of IPI-145 defined as the optimal dose at which ≤1 of 6 patients experiences a DLT assessed by NCI CTCAE v4.0.

  up to 12 months

Secondary Outcomes (1)

• Antitumor activity

  Up to 5 years

Other Outcomes (3)

• PK of IPI-145 and its metabolites

  Day 1

• PDx of IPI-145

  Up to 12 months

• Molecular predictors of IPI-145

  Up to 12 months

Study Arms (2)

Arm 1: IPI-145 plus Rituximab

EXPERIMENTAL

IPI-145 will be administered orally, twice daily, in 28-day (4-week) cycles, on a continuous basis at the maximum tolerated dose of 25 mg twice-daily (BID), as determined in the dose escalation phase. Twelve (12) cycles of IPI-145 will be administered. Patients who benefit from treatment may continue on study for additional cycles until toxicity or progressive disease. Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Day 1 once weekly during a 28 day cycle; 2 cycles of rituximab will be administered.

Drug: IPI-145; Drug: Rituximab

Arm 2: IPI-145 plus Rituximab/Bendamustine

EXPERIMENTAL

IPI-145 will be administered orally, twice daily, in 28 day cycles, on a continuous basis, until disease progression, unacceptable toxicity or patient refusal. The maximum tolerated dose of IPI-145 will be 25 mg twice-daily (BID) as determined in the dose escalation phase. Twelve (12) cycles of IPI-145 will be administered. Patients who benefit from treatment may continue on study for additional cycles until toxicity or progressive disease. Rituximab 375 mg/m2 will be administered intravenously (IV) beginning on Day 1 once weekly of each 28 day cycle. A maximum of 6 cycles of rituximab will be given. Bendamustine 90 mg/m2 IV will be administered on Days 1 and 2, of each 28 day cycle. Rituximab should be administered prior to bendamustine.

Drug: IPI-145; Drug: Rituximab; Drug: Bendamustine

Interventions

IPI-145 DRUG

Also known as: Duvelisib

Arm 1: IPI-145 plus Rituximab; Arm 2: IPI-145 plus Rituximab/Bendamustine

Rituximab DRUG

Also known as: Rituxan

Arm 1: IPI-145 plus Rituximab; Arm 2: IPI-145 plus Rituximab/Bendamustine

Bendamustine DRUG

Also known as: Treanda

Arm 2: IPI-145 plus Rituximab/Bendamustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose Escalation Phase
• Arm 1 and Arm 2: Limited to subjects diagnosed with low grade CD-20 positive B-Cell NHL with at least one prior anticancer treatment.
• Dose Expansion Phase
• Arm 1 Cohort A: Limited to subjects with CD-20 positive CLL with at least one prior anticancer treatment.
• Arm 1 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at least one prior anticancer treatment.
• Arm 2 Cohort A: Limited to subjects with CD-20 positive CLL with at least one prior anticancer treatment.
• Arm 2 Cohort B: Limited to subjects with diagnosis of CD-20 positive NHL with at least one prior anticancer treatment.
• Disease status requirement:
• CLL subjects: symptomatic disease that mandate treatment;
• Indolent NHL subjects: symptomatic disease requiring treatment according to the clinical judgment of the investigator;
• Other lymphoma subjects: disease requiring treatment according to the judgment of the investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤2.
• Subject must have measurable disease using the disease-specific response criteria for NHL or CLL
• Age ≥ 18 years.
• Subject has recovered from all clinically significant toxicities related to prior antineoplastic therapies with the exception of alopecia and bone marrow and organ functions.

You may not qualify if:

• Prior allogeneic hematopoietic stem cell transplant (HSCT).
• Prior autologous transplant or radioimmunotherapy ≤6 months prior to the first dose of trial treatment.
• Subject has a high grade lymphoma such as Burkitt's, lymphoblastic or small non-cleaved cell lymphomas. Subjects with intermediate grade lymphoma (such as diffuse large B-cell lymphoma) are eligible.
• Subjects with diffuse B-cell lymphoma must either not be eligible for autologous bone marrow transplant (BMT) or relapsed after autologous BMT.
• More than three previous cytotoxic chemotherapy regimens for subjects treated on the arm containing bendamustine.
• Subjects who have had a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies.
• Chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), radiation therapy (other than whole brain irradiation \[WBI\]) surgery or ablative therapy or investigational drugs/devices ≤28 days before first dose of trial treatment.
• Subjects receiving high doses of corticosteroids must have been tapered to a stable dose at least 7 days before the first dose of trial treatment.
• Tyrosine kinase inhibitor within 7 days prior to the first dose of trial treatment.
• Subjects with overt leptomeningeal leukemia or central nervous system (CNS) lymphoma. Subjects must be free of CNS disease for a minimum of 2 months. Subjects with symptoms of CNS disease must have a negative diagnostic lumbar puncture prior to study enrollment.
• Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
• Baseline QTcF \>480 ms. Note: This criterion does not apply to subjects with a left bundle branch block.
• Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria:
• Have been on a stable dose of anticoagulation for \<1 month.
• Have had a Grade 2, 3 or 4 hemorrhages in the last 30 days.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Infinity Pharmaceuticals, Inc.: collaborator

Study Sites (4)

The Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Hematologic Neoplasms; Recurrence

Interventions

duvelisib; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ian Flinn, M.D.

  SCRI

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2013
• First Posted: June 7, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: July 11, 2016

Record last verified: 2016-07

Locations

US (4)