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

NCT ID: NCT02352558

Last Updated: 2023-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2019-05-16

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Patients with multiple myeloma treated with BBI608

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Arm 2

Patients with lymphoma treated with BBI608

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Arm 3

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

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Arm 4

Patients with chronic myeloid leukemia treated with BBI608

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Arm 5

Patients with multiple myeloma treated with BBI608 and dexamethasone

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Dexamethasone

Intervention Type: 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 6

Patients with multiple myeloma treated with BBI608 and bortezomib

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Bortezomib

Intervention Type: 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).

Arm 7

Patients with chronic myeloid leukemia treated with BBI608 and imatinib

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Imatinib

Intervention Type: 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.

Arm 8

Patients with chronic lymphocytic leukemia treated with BBI608

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Arm 9

Patients with chronic lymphocytic leukemia treated with BBI608 and ibrutinib

Group Type: EXPERIMENTAL

BBI608

Intervention Type: 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.

Ibrutinib

Intervention Type: 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.

Interventions

BBI608

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.

Intervention Type: DRUG

Dexamethasone

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.

Intervention Type: DRUG

Bortezomib

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).

Intervention Type: DRUG

Imatinib

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.

Intervention Type: DRUG

Ibrutinib

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.

Intervention Type: DRUG

Other Intervention Names

Napabucasin; BB608; BBI-608; Velcade; Gleevec; Imbruvica

Eligibility Criteria

Inclusion Criteria

1. 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

2. A histologically confirmed hematologic malignancy that is advanced, relapsed, or refractory to standard, currently available anti-cancer treatment options

3. ≥ 18 years of age

4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at dose escalation phase and of ≤ 2 at dose expansion phase

5. 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

6. Females of childbearing potential must have a negative serum pregnancy test

7. 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

8. 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

9. Life expectancy ≥ 3 months

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Indiana University

Indianapolis, Indiana, United States

West Clinic

Germantown, Tennessee, United States

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Cancer Care Centers of South Texas - HOAST

San Antonio, Texas, United States

Virginia Cancer Specialists, P.C.

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Northwest Cancer Specialists, PC

Vancouver, Washington, United States

Countries

United States

Other Identifiers

BBI608-103HEM

Identifier Type: OTHER

Identifier Source: secondary_id

BBI608-103HEME

Identifier Type: -

Identifier Source: org_study_id