Venetoclax and Ibrutinib in Patients With Relapsed/Refractory CLL or SLL

NCT03045328 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-36705NCI-2017-00124HEM0048
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label non-randomized two-center phase 2 study evaluating the safety and efficacy of concurrent therapy with ibrutinib and venetoclax in subjects with relapsed or refractory CLL/SLL.

Conditions

Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  Complete Response (CR) will be assessed as the number of participants who, based on investigator assessment based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, achieve a complete remission. IWCLL complete remission is defined as follows. * Lymphadenopathy: none \> 1.5 cm * Blood lymphocytes: \< 4,000/µL * Hepatomegaly: none * Splenomegaly: none * Bone marrow: normocellular with \< 30 lymphocytes, no B lymphoid nodules. The outcome is reported as the number of participants who achieve CR, a number without dispersion.

  62 weeks

Secondary Outcomes (6)

• Duration of Response (DoR)

  117 weeks

• Minimal Residual Disease (MRD)

  117 weeks

• Overall Response (OR)

  62 weeks

• Overall Survival (OS)

  Through 117 weeks

• Progression-free Survival (PFS)

  117 weeks

Other Outcomes (1)

• Time-to-next-treatment (TTNT)

  Through 117 weeks

Study Arms (1)

Treatment (ibrutinib, venetoclax)

EXPERIMENTAL

Patients receive ibrutinib PO QD beginning on week 1 day 1. Treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax PO QD beginning on week 9 day 1. Treatment with venetoclax continues up to week 61 day 7 in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Drug: Venetoclax

Interventions

Ibrutinib DRUG

Administered at 420 mg/day, as oral capsules (3 x 140 mg), starting Day 1, Week 1.

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, venetoclax)

Venetoclax DRUG

Administered as tablets, starting Day 1, Week 9, with dose increasing every 7 days through 5 dose levels (20 mg; 50 mg; 100 mg; 200 mg; 400 mg).

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta

Treatment (ibrutinib, venetoclax)

Eligibility Criteria

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

You may qualify if:

• Subject must voluntarily sign and date an informed consent approved by the Institutional Review Board prior to initiation of any study specific procedures
• Subject must have a diagnosis of CLL that meets International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute (NCI)-Working Group (WG) criteria
• Subject must have relapsed/refractory disease with an indication for treatment according to the 2008 IWCLL/NCI WG criteria
• Measurable nodal disease by computed tomography (CT)
• Absolute neutrophil count \> 750 cells/mm\^3 (0.75 x 10\^9/L)
• Platelet count \> 30,000 cells/mm\^3 (30 x 10\^9/L)
• Hemoglobin \> 8.0 g/dL
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) =\< 2.5 x upper limit of normal (ULN)
• Estimated creatinine clearance \>= 30 mL/min (Cockcroft-Gault)
• Bilirubin =\< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
• Prothrombin time/international normalized ratio (PT/INR) \< 1.5 x ULN and partial thromboplastin time (PTT) (activated \[a\]PTT) \< 1.5 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for \>= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing potential must have a negative serum pregnancy test upon study entry
• Male and female subjects must agree to use highly effective methods of birth control (eg, condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug

You may not qualify if:

• Subject has previously received either venetoclax or ibrutinib
• Subject has received a live virus vaccine within 28 days prior to the initiation of study treatment
• Subject has undergone an allogeneic stem cell transplant in the past 1 year and must not have active chronic graft versus host disease (cGVHD) if over 1 year post allogeneic transplant
• Subject has developed Richter's transformation confirmed by biopsy
• Chemotherapy =\< 21 days prior to first administration of study treatment and/or monoclonal antibody =\< 6 weeks prior to first administration of study treatment
• History of other malignancies, except:
• Malignancy treated with curative intent and with no known active disease present for \>= 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc, or chronic administration \[\> 14 days\] of \> 20 mg/day of prednisone) within 28 days of the first dose of study drug
• Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
• Recent infection requiring systemic treatment that was completed =\< 14 days before the first dose of study drug
• Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded

Sponsors & Collaborators

• Steven E. Coutre: lead

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

Location

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; venetoclax

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

Results Point of Contact

• Title: Steven Edward Coutre, Professor of Medicine (Hematology)
• Organization: Stanford University

coutre@stanford.edu

650-498-6000

Study Officials

• Steven Coutre

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 7, 2017
• Study Start: September 26, 2017
• Primary Completion: May 19, 2020
• Study Completion: August 5, 2021
• Last Updated: September 29, 2021
• Results First Posted: September 29, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)