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

Sponsor

Sumitomo Pharma Oncology, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02352558

Collaborator

(none)

Enrollment

Locations

Arms

48.5

Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancy	Drug: BBI608 Drug: Dexamethasone Drug: Bortezomib Drug: Imatinib Drug: Ibrutinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ib Clinical Study of BBI608 for Adult Patients With Advanced, Refractory Hematologic Malignancies

Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Dec 14, 2018

Actual Study Completion Date :

May 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Patients with multiple myeloma treated with BBI608	Drug: 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. Other Names: Napabucasin BB608 BBI-608
Experimental: Arm 2 Patients with lymphoma treated with BBI608	Drug: 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. Other Names: Napabucasin BB608 BBI-608
Experimental: Arm 3 Patients with acute myeloid leukemia or myelo-dysplastic syndrome treated with BBI608	Drug: 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. Other Names: Napabucasin BB608 BBI-608
Experimental: Arm 4 Patients with chronic myeloid leukemia treated with BBI608	Drug: 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. Other Names: Napabucasin BB608 BBI-608
Experimental: Arm 5 Patients with multiple myeloma treated with BBI608 and dexamethasone	Drug: 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. Other Names: Napabucasin BB608 BBI-608 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.
Experimental: Arm 6 Patients with multiple myeloma treated with BBI608 and bortezomib	Drug: 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. Other Names: Napabucasin BB608 BBI-608 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). Other Names: Velcade
Experimental: Arm 7 Patients with chronic myeloid leukemia treated with BBI608 and imatinib	Drug: 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. Other Names: Napabucasin BB608 BBI-608 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. Other Names: Gleevec
Experimental: Arm 8 Patients with chronic lymphocytic leukemia treated with BBI608	Drug: 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. Other Names: Napabucasin BB608 BBI-608
Experimental: Arm 9 Patients with chronic lymphocytic leukemia treated with BBI608 and ibrutinib	Drug: 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. Other Names: Napabucasin BB608 BBI-608 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. Other Names: Imbruvica

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on patient blood samples collected on-study, as well as on (if available) bone marrow, other biopsied patient tumor tissue, and archival samples.
Assessment of the preliminary anti-tumor activity by performing tumor assessments [20 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Major Inclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
2	Indiana University	Indianapolis	Indiana	United States	46202
3	West Clinic	Germantown	Tennessee	United States	38138
4	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78217
5	Cancer Care Centers of South Texas - HOAST	San Antonio	Texas	United States	78229
6	Virginia Cancer Specialists, P.C.	Fairfax	Virginia	United States	22031
7	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
8	Northwest Cancer Specialists, PC	Vancouver	Washington	United States	98684