A Clinical Trial of Buparlisib and Ibrutinib in Lymphoma

NCT02756247 | Completed Phase 1

• 1 other identifier: 16-009
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to find out if the combination of buparlisib and ibrutinib will lead to better treatment results in patients with relapsed or refractory Follicular lymphoma, (FL) Mantle cell lymphoma (MCL) or Diffuse Large B-cell lymphoma (DLBCL). The investigators are using buparlisib and ibrutinib because both drugs seem to block different proteins that allow cancer cells to keep growing. Blocking these proteins may help by making the cancer cells undergo cell death, which will stop uncontrolled tumor growth.

Conditions

Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma; Diffuse Large B Cell Lymphoma

Keywords

Buparlisib; BKM120; Ibrutinib; 16-009

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  In the Phase I part the standard 3+3 dose escalation scheme will be used and all disease subtypes will be combined. If none of the initial cohort of 3 has a DLT the dose level will be escalated. If one has a DLT that dose level will be expanded with 3 more patients. Dose escalation will stop if 2 or more DLTs are seen at a dose level. The MTD is defined as the highest dose level at which at most 1 of the 6 patients treated at that level has a DLT. Three dose levels plus a "-1" dose level are planned for this study.

  1 year

Study Arms (1)

Buparlisib and Ibrutinib

EXPERIMENTAL

This is a two stage protocol comprised of a single institution phase Ib dose escalation trial. The first stage is a standard 3+3 phase I dose escalation trial to assess the safety of buparlisib and ibrutinib. The second stage is a single center expansion cohort in MCL, FL and DLBCL respectively evaluating the efficacy of buparlisib and ibrutinib combination. Treatment will be with ibrutinib orally daily and buparlisib orally daily. A cycle is defined as 4 weeks of therapy. Therapy will continue until disease progression, intolerable toxicities or death with a maximum duration for 36 cycles, not exceeding 36 months on therapy.

Drug: Buparlisib; Drug: Ibrutinib

Interventions

Buparlisib DRUG

Buparlisib and Ibrutinib

Ibrutinib DRUG

Buparlisib and Ibrutinib

Eligibility Criteria

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

You may qualify if:

• Patient is ≥ 18 years of age at the time of signing Informed Consent
• Patient is able and willing to adhere to the study visit schedule and other protocol requirements
• Patient has histologically confirmed diagnosis of R/R mantle cell lymphoma, follicular lymphoma or diffuse large B cell lymphoma
• Diffuse large B cell lymphoma patients has received at least 1 prior regimen and received, declined, or is ineligible for autologous or allogeneic stem cell transplant.
• Follicular lymphoma patients have received at least 2 lines of therapy.
• Mantle cell lymphoma patients has received at least 1 line of therapy
• Allogeneic stem cell transplant recipients be greater than 6 months post transplant, not on immunosuppression for prevention of graft versus host disease for \>3 months and without active graft versus host disease are eligible
• Autologous stem cell transplant recipients must have adequate bone marrow recovery and transfusion independent
• Transformed histologies are permitted
• Patient has at least one measurable lesion (≥ 2 cm) according to Lugano Classification
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Patient has adequate bone marrow and organ function by:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L , independent of growth factor support unless with bone marrow involvement for 14 days
• Platelets ≥100 x 109/L, or ≥50 x 10\^9/L if bone marrow involvement and independent of transfusion support for 14 days in either situation
• Hemoglobin (Hgb) ≥ 9.0 g/dL (no RBC transfusion within past 14 days)

You may not qualify if:

• Patients previously treated with ibrutinib or PI3K inhibitor
• Patient has a history of non-compliance to medical regimen or inability to grant consent
• Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
• Patient is concurrently using other approved or investigational antineoplastic agent
• Patient has had major surgery or a wound that has not fully healed within 4 weeks of starting study drugs.
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
• Patient has evidence of active graft versus host disease (GVHD)
• Patient has active or history of central nervous system (CNS) disease or meningeal involvement.
• Patient has history of stroke or intracranial hemorrhage ≤ 6 months from starting study drugs.
• Patient has a score ≥ 12 on the PHQ-9 questionnaire, selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9), score ≥ 15 on GAD-7 mood scale.
• Patient has ≥ CTCAE grade 3 anxiety Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, homicidal ideation (e.g. risk of doing harm to self or others)
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• Patient has clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification. Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO), unstable angina pectoris, symptomatic pericarditis, QTcF \> 480 msec on the screening ECG (using the QTcF formula)
• Patient has a concurrent active malignancy. Malignancies treated with a curative intent with an expected life expectancy ≥ 5 years or a non-competing life expectancy risk are eligible (i.e. adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, early stage breast cancer, treated prostate cancer or any other cancer from which the patient has been disease free for \>/= 3 years).
• Patient with known history of human immunodeficiency virus (HIV), or any uncontrolled active systemic infection.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Scientific Affairs, LLC: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (6)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Stewart CM, Michaud L, Whiting K, Nakajima R, Nichols C, De Frank S, Hamlin PA Jr, Matasar MJ, Gerecitano JF, Drullinsky P, Hamilton A, Straus D, Horwitz SM, Kumar A, Moskowitz CH, Moskowitz A, Zelenetz AD, Rademaker J, Salles G, Seshan V, Schoder H, Younes A, Tsui DWY, Batlevi CL. Phase I/Ib Study of the Efficacy and Safety of Buparlisib and Ibrutinib Therapy in MCL, FL, and DLBCL with Serial Cell-Free DNA Monitoring. Clin Cancer Res. 2022 Jan 1;28(1):45-56. doi: 10.1158/1078-0432.CCR-21-2183. Epub 2021 Oct 6.

  PMID: 34615723 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse

Interventions

NVP-BKM120; ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Study Officials

• Connie Batlevi, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: April 29, 2016
• Study Start: May 9, 2016
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: October 10, 2022

Record last verified: 2022-10

Locations

US (6)