Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

NCT02332980 | Completed Phase 2 Results DMC

• 4 other identifiers: MC1485NCI-2014-02561P50CA09727414-005666
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well pembrolizumab alone or with idelalisib or ibrutinib works in treating patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas that have returned after a period of improvement (relapsed) or have not responded to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Idelalisib and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab alone or with idelalisib or ibrutinib may be an effective treatment in patients with chronic lymphocytic leukemia or other low-grade B-cell non-Hodgkin lymphomas.

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Refractory Waldenstrom Macroglobulinemia; Richter Syndrome; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Who Achieve a Confirmed Response

  Confirmed response is defined to be a partial response, nodular partial response, clinical complete response, confirmed response with incomplete blood count recovery or confirmed response (Arm A and B), or complete metabolic response, partial metabolic response, partial response, or confirmed response (Arm C). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial confidence intervals for the true success proportion will be calculated.

  1 year

Secondary Outcomes (11)

• Progression-free Survival of Patients Treated in Single Agent Phase

  5 years

• Progression-free Survival of Patients Treated With Combination Therapy

  5 years

• Treatment-free Survival of Patients Treated With Single-agent Pembrolizumab

  5 years

• Treatment-free Survival of Patients Treated With Combination Therapy

  5 years

• Time to Next Treatment for Patients Treated With Single-agent Pembrolizumab

  5 years

Other Outcomes (5)

• PD-1 Levels

  Up to 1 year

• PD-L1 Levels

  Up to 1 year

• PD-L2 Levels

  Up to 1 year

Study Arms (1)

Treatment (pembrolizumab, idelalisib, or ibrutinib)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients receiving benefit may continue to receive treatment for an additional 12 months at the discretion of the investigator. Patients with CLL or CLL with Richter's transformation experiencing stable disease without partial remission or progressive disease at 3 months of treatment with pembrolizumab proceed to the treatment continuation phase. CONTINUATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Patients also receive idelalisib PO BID on days 1-21 OR ibrutinib PO QD on days 1-21. Treatment repeats every 21 days for up to 12 or 24 months in the absence of disease progression or unacceptable toxicity. Patients receiving benefit may continue to receive treatment for an additional 12 months at the discretion of the investigator.

Drug: Ibrutinib; Drug: Idelalisib; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Ibrutinib DRUG

Given PO

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

Treatment (pembrolizumab, idelalisib, or ibrutinib)

Idelalisib DRUG

Given PO

Also known as: CAL-101, GS 1101, GS-1101, Phosphoinositide-3 Kinase Delta Inhibitor CAL-101, Zydelig

Treatment (pembrolizumab, idelalisib, or ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, idelalisib, or ibrutinib)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, idelalisib, or ibrutinib)

Eligibility Criteria

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

You may qualify if:

• CLL/SLL PATIENTS (ARM A) ONLY
• Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria; this includes previous documentation of:
• Biopsy-proven small lymphocytic lymphoma or
• Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:
• Peripheral blood B cell count of \> 5 x 10\^9/L consisting of small to moderate size lymphocytes
• Immunophenotyping consistent with CLL defined as:
• The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation \[CD\]19, CD20 \[typically dim expression\] or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
• Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable \[IGHV\] analysis)
• NOTE: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
• Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescent in situ hybridization (FISH) analysis for t(11;14) (immunoglobulin H \[IgH\]/cyclin D1 \[CCND1\]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy
• Patients must be previously treated with at least one prior line of therapy; EXCEPTION: CLL patients with Richter's transformation or Hodgkin transformation do not need prior therapy to enroll
• NOTE:
• Prior chemotherapy or biologic novel therapy or anti-cancer monoclonal antibody based therapy for treatment of CLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments) will not be considered "prior treatment"
• Prior oral corticosteroid therapy for an indication other than CLL will not be considered "prior treatment"
• Previous use of corticosteroids in the combination with other therapy for treatment of autoimmune complications of CLL does constitute prior therapy for CLL

You may not qualify if:

• Currently participating in or has participated in a study of an investigational agent or using an investigational device =\< 28 days prior to registration
• Receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy =\< 7 days prior to registration; EXCEPTIONS:
• Low doses of steroids (=\< 20 mg of prednisone or equivalent dose of other steroid/day)
• Previous use of corticosteroids is allowed
• After initiation of MK-3475 therapy, steroid can be used for management of potential immune mediated adverse events (AE) for less than 8 weeks of therapy
• Topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) are permitted
• Prior anti-cancer monoclonal antibody =\< 28 days prior to registration or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Prior chemotherapy or radiation therapy =\< 14 days prior to registration or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Known additional malignancy that is progressing or requires active treatment; EXCEPTIONS (these following exceptions are permitted to enroll in this trial):
• Basal cell carcinoma or squamous cell carcinoma or melanoma of the skin that has undergone or will undergo potentially curative therapy
• In situ cervical cancer that has undergone or will undergo potentially curative therapy
• Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past; EXCEPTIONS:
• Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, Shanafelt TD, Sinha S, Le-Rademacher J, Feldman AL, Habermann TM, Witzig TE, Wiseman GA, Lin Y, Asmus E, Nowakowski GS, Conte MJ, Bowen DA, Aitken CN, Van Dyke DL, Greipp PT, Liu X, Wu X, Zhang H, Secreto CR, Tian S, Braggio E, Wellik LE, Micallef I, Viswanatha DS, Yan H, Chanan-Khan AA, Kay NE, Dong H, Ansell SM. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017 Jun 29;129(26):3419-3427. doi: 10.1182/blood-2017-02-765685. Epub 2017 Apr 19.

  PMID: 28424162 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Waldenstrom Macroglobulinemia

Interventions

ibrutinib; idelalisib; pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Wei Ding
• Organization: Mayo Clinic

Ding.Wei@mayo.edu

5072845096

Study Officials

• Wei Ding

  Mayo Clinic in Rochester

  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

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 7, 2015
• Study Start: February 19, 2015
• Primary Completion: August 10, 2021
• Study Completion: January 4, 2022
• Last Updated: January 3, 2024
• Results First Posted: March 21, 2023

Record last verified: 2023-12

Locations

US (2)