A Study of BNC105P Combined With Ibrutinib

NCT03454165 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D17093
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I Trial of BNC105P in combination with BTK inhibitor ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia(CLL). This study proposes that ibrutinib will have far greater efficacy when it is combined with drugs that kill the CLL cells in peripheral circulation, thereby preventing them from returning to the protective lymph node niche. The study will establish the maximum tolerated dose(MTD) of the combination of BNC105P with ibrutinib, characterize the pharmacodynamic effects of BNC105P alone and in combination with ibrutinib in CLL cells, and provide preliminary assessment of the efficacy of the combination in CLL. The study consists of a Screening Period with baseline tumor assessment before BNC105P administration, a Treatment Period with up to six 21-day cycles and Follow-up Period. Subjects will receive a total of six cycles of therapy unless treatment is discontinued

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• To establish the maximum tolerated dose and toxicity of BNC105P plus Ibrutinib

  The number of relapsed refractory chronic lymphatic leukemia patients, in cohorts of 3-6, who develop treatment related adverse effects from combined therapy with BNC105P and ibrutinib. The treatment related adverse events will be defined based on CTCAE v 4.0

  Two years

Secondary Outcomes (3)

• Evaluating the efficacy of BNC105P combined with Ibrutinib in patients with CLL

  Two years

• Determine the Overall Response Rate (ORR)

  Two years

• Determine the event free survival

  Two years

Other Outcomes (1)

• Explore the effects of BNC105P and BNC105P + Ibrutinib on NOXA and JNK in Chronic Lymphocytic Leukemia Cells

  Two years

Study Arms (1)

Single Arm

EXPERIMENTAL

Evaluate the MTD of BNC105P in combination with ibrutinib in patients with relapsed/refractory CLL. Treatment will be administered on an outpatient basis but will also be permitted inpatient. BNC105P will be administered as a single agent prior to initiation of ibrutinib. Beginning with cycle 2, ibrutinib will be administered concomitantly with BNC105P at a starting dose of 420 mg PO daily. Each cycle will last for 21 days. Provided no toxicities occur, each patient will be treated for 6 cycles.

Combination Product: BNC105P; Combination Product: Ibrutinib

Interventions

BNC105P COMBINATION_PRODUCT

BNC105P is the phosphate ester of BNC105, a small molecule tubulin polymerization inhibitor.

Single Arm

Ibrutinib COMBINATION_PRODUCT

A novel BTK inhibitor.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Patients who are \> 18 years of age, must have histologically or flow cytometry confirmed diagnosis of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) according to NCI-WG 1996 guidelines. The malignant B cells must co-express CD5 with CD19 or CD20. Patients who lack CD23 expression on their leukemia cells should be examined for (and found NOT to have) either t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma. Patients with CLL who have progressed on prior ibrutinib therapy will be eligible. Patients with B-cell prolymphocytic leukemia and patients with Richter's transformation of CLL/SLL are NOT eligible.
• Active disease meeting at least 1 of the IWCLL 2008 criteria for requiring treatment:
• i) A minimum of any one of the following constitutional symptoms:
• Unintentional weight loss \>10% within the previous 6 months prior to screening.
• Extreme fatigue (unable to work or perform usual activities).
• Fevers of greater than 100.5 F for ≥2 weeks without evidence of infection.
• Night sweats without evidence of infection. ii) Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia.
• iii) Massive (i.e., \>6 cm below the left costal margin), progressive or symptomatic splenomegaly.
• iv) Massive nodes or clusters (i.e., \> 10 cm in longest diameter) or progressive lymphadenopathy.
• v) Progressive lymphocytosis with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months.
• vi) Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids.
• Patients must have received at least one prior therapy for CLL comprised of the following:
• i) ≥1 regimen containing an anti-CD20 antibody (e.g., rituximab, obinutuzumab) administered for ≥ 2 doses ii) ≥1 regimen containing ≥1 cytotoxic agent (eg, bendamustine, fludarabine, chlorambucil, cyclophosphamide) administered for ≥ 2 cycles
• Patients must have ECOG performance status ≤2.
• Patients must have organ function as defined below:

You may not qualify if:

• Prior therapeutic intervention with any of the following:
• nitrosoureas or mitomycin C within 6 weeks;
• therapeutic anticancer antibodies (including rituximab) within 4 weeks;
• radio- or toxin-immunoconjugates within 10 weeks;
• all other chemotherapy, radiation therapy within 3 weeks prior to initiation of therapy.
• Inadequate recovery from adverse events related to prior therapy to grade ≤1 (excluding Grade 2 alopecia and neuropathy).
• Chronic use of corticosteroids in excess of prednisone 20 mg/day or its equivalent.
• Stem cell transplant recipients must have no evidence of active graft-versus-host disease.
• Use of full dose, therapeutic anti-coagulation with warfarin.
• Concomitant use of strong CYP inducers or inhibitors including nutraceutical preparations, e.g., grapefruit juice and St John's Wort
• History prior malignancy except:
• Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study;
• adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease;
• adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease;
• asymptomatic prostate cancer managed with "watch and wait" strategy;

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

BNC 105P; ibrutinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Lionel D Lewis, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Pharmacology/Toxicolgy

Model Details: Open label dose escalation study, with a Storer D ; 3-3 cohort design

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: March 5, 2018
• Study Start: March 9, 2018
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: January 4, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)