A Study of BBI608 in Adult Patients With Advanced, Refractory Hematologic Malignancies

NCT02352558 | Completed Phase 1

• 2 other identifiers: BBI608-103HEMEBBI608-103HEM
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multicenter, open label, Phase 1 dose-escalation study of BBI608 administered to patients with relapsed, refractory hematologic malignancies, including multiple myeloma, lymphoma, and others.

Conditions

Hematologic Malignancy

Keywords

Multiple Myeloma; Lymphoma; Acute Myeloid Leukemia; Myelo-Dysplastic Syndrome; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Determination of the safety and tolerability of BBI608 administered as monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib by assessing dose-limiting toxicities (DLTs)

  4 weeks

Secondary Outcomes (3)

• Pharmacokinetic profile of BBI608 when administered in monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib as assessed by maximum plasma concentration and area under the curve

  -5min, 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 11, 12 hours on day 1, cycles 1 and 2

• Pharmacodynamic activity of BBI608 when administered in monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib as assessed by biomarker analysis

  20 weeks

• Assessment of the preliminary anti-tumor activity by performing tumor assessments

  20 weeks

Study Arms (9)

Arm 1

EXPERIMENTAL

Patients with multiple myeloma treated with BBI608

Drug: BBI608

Arm 2

EXPERIMENTAL

Patients with lymphoma treated with BBI608

Drug: BBI608

Arm 3

EXPERIMENTAL

Patients with acute myeloid leukemia or myelo-dysplastic syndrome treated with BBI608

Drug: BBI608

Arm 4

EXPERIMENTAL

Patients with chronic myeloid leukemia treated with BBI608

Drug: BBI608

Arm 5

EXPERIMENTAL

Patients with multiple myeloma treated with BBI608 and dexamethasone

Drug: BBI608; Drug: Dexamethasone

Arm 6

EXPERIMENTAL

Patients with multiple myeloma treated with BBI608 and bortezomib

Drug: BBI608; Drug: Bortezomib

Arm 7

EXPERIMENTAL

Patients with chronic myeloid leukemia treated with BBI608 and imatinib

Drug: BBI608; Drug: Imatinib

Arm 8

EXPERIMENTAL

Patients with chronic lymphocytic leukemia treated with BBI608

Drug: BBI608

Arm 9

EXPERIMENTAL

Patients with chronic lymphocytic leukemia treated with BBI608 and ibrutinib

Drug: BBI608; Drug: Ibrutinib

Interventions

BBI608 DRUG

Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.

Also known as: Napabucasin, BB608, BBI-608

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5; Arm 6; Arm 7; Arm 8; Arm 9

Dexamethasone DRUG

Dexamethasone will be taken orally at a dose level of 40 mg once weekly, on Days 1, 8, 15, and 22 of each Cycle. Patients over the age of 75 years are allowed to begin dexamethasone at a dose of 20 mg once weekly, on Days 1, 8, 15, and 22 of each Cycle. Dexamethasone should be taken with food or milk, and a minimum of 2 hours should separate a dose of dexamethasone from a dose of BBI608.

Arm 5

Bortezomib DRUG

Bortezomib will be administered at 1.3 mg/m2/dose as a 3-5 second bolus intravenous (IV) injection or subcutaneous injection twice weekly for 2 weeks (Day 1, 4, 8, and 11) followed by a 10-day rest period (Day 12-21).

Also known as: Velcade

Arm 6

Imatinib DRUG

Imatinib will be taken orally once daily with a meal and a large glass of water. For patients having difficulty swallowing, imatinib can be dissolved in water or apple juice for intake. The dose of imatinib is 400 mg for CML patients in the chronic phase and 600 mg for CML patients in the accelerated phase or in blast crisis. A minimum of 2 hours should separate a dose of imatinib from a dose of BBI608.

Also known as: Gleevec

Arm 7

Ibrutinib DRUG

Ibrutinib will be taken orally once daily with water. Do not open, break, or chew the capsules. The dose of ibrutinib is 420 mg for patients with normal liver function and is 140 mg for patients with mild liver impairment (Child-Pugh class A). A minimum of 2 hours should separate a dose of ibrutinib from a dose of BBI608.

Also known as: Imbruvica

Arm 9

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent must be obtained and documented according to the International Conference on Harmonisation (ICH) and be in accordance with local regulatory requirements
• A histologically confirmed hematologic malignancy that is advanced, relapsed, or refractory to standard, currently available anti-cancer treatment options
• ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at dose escalation phase and of ≤ 2 at dose expansion phase
• Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after their last dose
• Females of childbearing potential must have a negative serum pregnancy test
• Aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN). Patients whose disease involves the liver and who have laboratory values of AST ≤ 3.5 ULN, AST ≤ 3.5 ULN, and albumin ≥ 35g/L may be enrolled if agreed upon by the Principal Investigator and Medical Monitor for the Sponsor
• Total bilirubin \< 1.5 x ULN, except for cases in which elevation of total bilirubin is due to elevated levels of unconjugated bilirubin consistent with a diagnosis of Gilbert's Syndrome
• Life expectancy ≥ 3 months

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (8)

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

West Clinic

Germantown, Tennessee, 38138, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78217, United States

Location

Cancer Care Centers of South Texas - HOAST

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists, P.C.

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Northwest Cancer Specialists, PC

Vancouver, Washington, 98684, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Multiple Myeloma; Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

napabucasin; Dexamethasone; Bortezomib; Imatinib Mesylate; ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Pyrimidines

Study Design

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

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: February 2, 2015
• Study Start: May 1, 2015
• Primary Completion: December 14, 2018
• Study Completion: May 16, 2019
• Last Updated: November 14, 2023

Record last verified: 2023-11

Locations

US (8)