Clinical Trials /

Rituximab and Pembrolizumab With or Without Lenalidomide in Treating Patients With Relapsed Follicular Lymphoma and Diffuse Large B-Cell Lymphoma

NCT02446457

Description:

This phase II trial studies how well rituximab and pembrolizumab with or without lenalidomide works in treating patients with follicular lymphoma and diffuse large B-cell lymphoma that has returned after a period of improvement. Immunotherapy with monoclonal antibodies, such as rituximab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rutuximab with pembrolizumab and lenalidomide may work better at treating follicular lymphoma and diffuse large B-cell lymphoma.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects With Relapsed Follicular Lymphoma
  • Official Title: Phase II Study of Rituximab Plus Pembrolizumab (MK-3475) in Subjects With Relapsed Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 2014-0539
  • SECONDARY ID: 0856-15
  • SECONDARY ID: NCI-2015-01307
  • NCT ID: NCT02446457

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
RituximabRituxanRituximab + Pembrolizumab
PembrolizumabKeytruda, MK-3475, SCH-900475Rituximab + Pembrolizumab

Purpose

The goal of this clinical research study is to learn if the combination of pembrolizumab and rituximab can help to control relapsed FL. The safety of this combination will also be studied.

Detailed Description

      Study Drug Administration:

      If you are found to be eligible for this study, you will receive rituximab and pembrolizumab
      in 21-day study cycles.

      On Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycle 2, you will receive rituximab by vein.
      The first infusion takes 6-8 hours. After that, infusions take about 4 hours each.

      On Day 2 of Cycles 1 and 2 and on Day 1 of Cycles 3-16, you will receive pembrolizumab by
      vein over 1 hour.

      Study Visits:

      On Day 1 of Cycle 1, your vital signs will be recorded.

      On Day 22 of Cycle 2, you will have a physical exam.

      On Day 1 of Cycles 3-16:

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests. Every 2 cycles, part of
           this sample will also be used to check your thyroid function. Every 4 cycles, part of
           this sample will also be used to check the status of your immune system.

      On Day 1 of Cycles 5, 9, and 13:

        -  Urine will be collected for routine tests.

        -  You will have a CT scan to check the status of the disease (Cycle 5 only).

      On Day 1 of Cycle 8, you will have a PET/CT scan to check the status of the disease.

      At any time, if your doctor think it is needed, you may have a bone marrow biopsy and
      aspirate and/or a CT or PET/CT scan to check the status of the disease.

      Length of Study:

      You may take rituximab for 2 cycles and pembrolizumab for up to 16 cycles. You will no
      longer be able to receive the drugs if the disease gets worse, if intolerable side effects
      occur, or if you are unable to follow study directions.

      Your participation on the study will be over once you have completed follow-up.

      End-of-Treatment Visit:

      After you stop receiving the study drug(s):

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests.

        -  If your doctor thinks it is needed, you will have a PET/CT scan to check the status of
           the disease.

      Long Term Follow-Up:

      30 days after your End-of-Treatment visit:

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests, to check your thyroid
           function, and to check the status of your immune system.

        -  Urine will be collected for routine tests.

      Every 3 months for 1 year and every 6 months after that until you start a new therapy, the
      disease gets worse, or the study ends:

        -  You will have a physical exam.

        -  Blood (about 2 tablespoons) will be drawn for routine tests, to check your thyroid
           function, and to check the status of your immune system.

        -  You will have a CT scan to check the status of the disease.

      This is an investigational study. Pembrolizumab is FDA approved and commercially available
      for the treatment of melanoma. Rituximab is FDA approved and commercially available for the
      treatment of non-Hodgkin's lymphoma and certain types of leukemia. The combination of these
      drugs to treat FL is investigational. The study doctor can describe how the study drugs are
      designed to work.

      Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Rituximab + PembrolizumabExperimentalParticipants receive Rituximab 375 mg/m2 by vein weekly for 4 weeks, and Pembrolizumab 200 mg by vein every 3 weeks for a maximum of 16 infusions. Study cycle is 21 days.
  • Rituximab
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female subjects with histologic proof of follicular lymphoma grade 1, grade
             2, or grade 3a relapsing after at least one prior systemic therapy that included
             rituximab. Patients should have rituximab-sensitive disease defined as a documented
             complete or partial response lasting at least 6 months after the last rituximab-based
             therapy.

          2. Either the subject or his/her legally authorized representative be willing and able
             to provide written informed consent for the trial.

          3. Be >/= 18 years of age on day of signing informed consent.

          4. Have measurable disease (>/= 1.5 cm in the longest diameter for nodal or extranodal
             disease).

          5. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale.

          6. Demonstrate adequate organ function as defined below, all screening labs should be
             performed within 28 days of treatment initiation. Hematological: Absolute neutrophil
             count (ANC) >/=1.0 × 10^9/L; Platelets >/=75 × 10^9/L; Hemoglobin >/= 8.0 g/dL; Serum
             creatinine OR Measured or calculated creatinine clearance (GFR can also be used in
             place of creatinine or CrCl) (Creatinine clearance will be calculated per
             institutional standard.) </=1.5 × upper limit of normal (ULN) OR >/=60 mL/min GFR or
             CrCl for subjects with creatinine levels > 1.5 × institutional ULN; Hepatic: Serum
             total bilirubin </= 1.5 × ULN OR Direct bilirubin </= ULN for subjects with total
             bilirubin levels > 1.5 ULN;

          7. #6 cont...aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase
             (SGOT) and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT)
             </= 2.5 × ULN OR </= 5 × ULN for subjects with lymphoma in the liver; Coagulation:
             International Normalized Ratio (INR) or Prothrombin Time (PT) </=1.5 × ULN unless
             subject is receiving anticoagulant therapy as long as PT or Partial Thromboplastin
             Time (PTT) is within therapeutic range of intended use of anticoagulants; Activated
             Partial Thromboplastin Time (aPTT) </=1.5 × ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended
             use of anticoagulants

          8. Female subject of childbearing potential should have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication.
             If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required.

          9. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of study medication. Female
             subjects of childbearing potential are those who have not been surgically sterilized
             or have not been free from menses for > 1 year.

         10. Male subjects should agree to use two methods of contraception starting with the
             first dose of study therapy through 120 days after the last dose of study therapy.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study drug or using an investigation device
             within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of
             trial treatment.

          3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has
             not recovered (i.e., </= Grade 1 or at baseline) from AEs due to agents administered
             more than 4 weeks earlier.

          4. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at
             baseline) from AEs 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.

          5. Has a known additional malignancy that is progressing and requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          6. Has known active central nervous system (CNS) lymphoma and/or lymphomatous
             meningitis. Subjects with previously treated CNS lymphoma and/or lymphomatous
             meningitis may participate provided they are stable (without evidence of progression
             by imaging for at least four weeks prior to the first dose of trial treatment and any
             neurologic symptoms have returned to baseline), have no evidence of new or enlarging
             brain metastases, and are not using steroids for at least 7 days prior to trial
             treatment.

          7. No active autoimmune disease that has required systemic treatment in past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment. Subjects with vitiligo or resolved childhood asthma/atopy
             would be an exception to this rule. Subjects that require intermittent use of
             bronchodilators, local steroid injections or inhaled or topical steroids would not be
             excluded from the study. Subjects with hypothyroidism stable on hormone replacement
             or Sjorgen's syndrome will not be excluded from the study.

          8. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

          9. Has an active infection requiring systemic therapy.

         10. Has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the trial, interfere with the
             subject's participation for the full duration of the trial, or is not in the best
             interest of the subject to participate, in the opinion of the treating investigator.

         11. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         12. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         13. .Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
             anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
             ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
             or checkpoint pathways).- Note: Subjects that received prior therapy with pidilizumab
             are an exception to this criterion and may qualify for the study.

         14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         16. Has received a live vaccine within 30 days prior to the first dose of trial
             treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (OR) in Participants with Relapsed Follicular Lymphoma with Pembrolizumab in Combination with Rituximab
Time Frame:24 weeks
Safety Issue:
Description:Overall response rate defined as complete plus partial responses. Overall response assessed after completion of 8 treatments with pembrolizumab and 4 doses of rituximab. OR monitored simultaneously using Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Disease response assessments performed by CT scans or PET-CT scan.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Lymphoma
  • Follicular lymphoma
  • FL
  • Relapsed
  • Rituximab
  • Rituxan
  • Pembrolizumab
  • Keytruda
  • MK-3475
  • SCH-900475

Last Updated

March 7, 2017