Clinical Trials /

Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

NCT03798314

Description:

This phase I trials studies side effects and best dose of pomalidomide when given together with nivolumab in treating patients with primary central nervous system diffuse large B cell lymphoma or primary vitreoretinal diffuse large B cell lymphoma that has come back or that has not responded to treatment. Immunotherapy with monoclonal antibodies, such as pomalidomide and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma
  • Official Title: Phase I Clinical Trial for Evaluation of Nivolumab and Pomalidomide Combination for Relapsed/Refractory Primary Central Nervous System Lymphoma and Primary Vitreoretinal Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: MC178A
  • SECONDARY ID: NCI-2018-03661
  • SECONDARY ID: MC178A
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03798314

Conditions

  • Recurrent Nervous System Lymphoma
  • Recurrent Primary Vitreoretinal DLBCL
  • Refractory Nervous System Lymphoma
  • Refractory Primary Vitreoretinal DLBCL

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab and pomalidomide)
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystTreatment (nivolumab and pomalidomide)

Purpose

This phase I trials studies side effects and best dose of pomalidomide when given together with nivolumab in treating patients with primary central nervous system diffuse large B cell lymphoma or primary vitreoretinal diffuse large B cell lymphoma that has come back or that has not responded to treatment. Immunotherapy with monoclonal antibodies, such as pomalidomide and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To establish the maximum tolerated dose (MTD) of pomalidomide which can be safely combined
      with the fixed dose schedule of nivolumab in patients with relapsed/refractory primary
      central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL). (Phase I)

      SECONDARY OBJECTIVES:

      I. To evaluate the overall response rate (ORR) and progression free survival (PFS) of
      nivolumab and pomalidomide combination in patients with relapsed/refractory PCNSL and PVRL.

      OUTLINE: This is dose-escalation study of pomalidomide.

      Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and pomalidomide
      orally (PO) on days 1-14. Treatment repeats every 4 weeks until disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 weeks, then every 3
      months for 4 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab and pomalidomide)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1 and pomalidomide PO on days 1-14. Treatment repeats every 4 weeks until disease progression or unacceptable toxicity.
  • Nivolumab
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Patient must have one of the following:

               -  Relapsed or refractory primary central nervous system (CNS) diffuse large B cell
                  lymphoma (PCNSDLBCL) with a brain lesion >= 1 cm, or with cerebrospinal fluid
                  (CSF) relapse with positive CSF cytology, or with ocular relapse with positive
                  ocular tissue biopsy

                    -  NOTE: Tissue biopsy is not absolutely necessary for brain tumor unless
                       clinical and radiologic findings strongly suggest other etiologies as per
                       treating physician. Initial diagnosis must be made by tissue biopsy OR

               -  Relapsed/refractory primary vitreoretinal diffuse large B cell lymphoma (DLBCL)
                  with a CNS lesion >= 1 cm, or with CSF relapse with positive CSF cytology, or
                  with ocular relapse with positive ocular tissue biopsy. Relapsed PVRL must have
                  progressed or failed at least one systemic regimen

                    -  NOTE: Intraocular treatments are not regarded as systemic therapy

                    -  NOTE: If recurrence in ocular or leptomeningeal space, the patient will need
                       a positive ocular tissue biopsy and CSF biopsy. Tissue biopsy requirement of
                       the CNS lesion is as outlined in bullet above

          -  Patient progressed after or did not respond to at least 1 line of systemic therapy
             (e.g., high-dose methotrexate, high-dose methotrexate based regimen, high dose
             cytarabine, etc)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (within =< 14 days prior to registration)

          -  Platelet count >= 100,000/mm^3 (within =< 14 days prior to registration)

          -  Hemoglobin >= 9.0 g/dL (within =< 14 days prior to registration)

          -  Direct bilirubin < 1.5 x upper limit of normal (ULN) (or total bilirubin =< 3.0 x ULN
             with direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert?s
             Syndrome) (within =< 14 days prior to registration)

          -  Aspartate transaminase (AST) =< 3 x ULN (within =< 14 days prior to registration)

          -  Creatinine =< 1.5 x ULN OR calculated creatinine clearance must be >= 45 ml/min using
             the Cockcroft-Gault formula (within =< 14 days prior to registration)

          -  Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time
             (PTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is
             within therapeutic range of intended use of anticoagulants (within =< 14 days prior to
             registration)

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 50 mIU/ml, =< 14 days prior to registration and
             within 24 hours of starting pomalidomide. In addition, must either commit to continue
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 28 days before she starts taking pomalidomide. WOCBP must also agree to
             ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact
             with a WOCBP even if they have had a vasectomy. In addition, women of childbearing
             potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception
             for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and
             who are sexually active with WOCBP will be instructed to adhere to contraception for a
             period of 7 months after the last dose of nivolumab. All patients must be counseled at
             a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

               -  A woman of childbearing potential is a sexually mature woman who: 1) has not
                  undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
                  postmenopausal for at least 24 consecutive months (i.e., has had menses at any
                  time in the preceding 24 consecutive months)

          -  Able to take aspirin (81 or 325 mg) daily or an anticoagulant (as determined by
             treating physician) as prophylactic anticoagulation

          -  Provide written informed consent

          -  Willingness to return to enrolling institution for follow-up (during the active
             monitoring phase of the study)

          -  Willingness to undergo biopsy procedures, if deemed necessary by treating physician

          -  Willing to be registered into a mandatory POMALYST REMS program, and willing and able
             to comply with the requirements of the POMALYST REMS program

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
             considered investigational (utilized for a non-Food and Drug Administration
             [FDA]-approved indication and in the context of a research investigation)

          -  Other active malignancy =< 3 years prior to registration

               -  EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix

               -  NOTE: If there is a history of prior malignancy, they must not have received
                  immune checkpoint inhibitors or immunomodulatory therapy (IMiD) for their cancer

          -  History of myocardial infarction =< 6 months prior to registration, or congestive
             heart failure requiring use of ongoing maintenance therapy for life-threatening
             ventricular arrhythmias

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

          -  Use of corticosteroid in the absence of cerebral edema

               -  NOTE: If a corticosteroid is used, it should be used at the lowest dose possible
                  for the shortest possible duration. Subjects with a condition requiring systemic
                  treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or
                  other immunosuppressive medications within 14 days of treatment assignment are
                  excluded

               -  EXCEPTIONS: Inhaled or topical steroids, and adrenal replacement steroid doses >
                  10 mg daily prednisone equivalent, are permitted in the absence of active
                  autoimmune disease

          -  Therapy with myelosuppressive chemotherapy or biologic therapy =< 21 days prior to
             registration with incomplete recovery of blood counts

          -  Persistent toxicities >= grade 3 from prior chemotherapy or biological therapy
             regardless of interval since last treatment

          -  History of thromboembolic episodes =< 3 months prior to registration

          -  Active hepatitis B or C with uncontrolled disease

               -  NOTE: A detailed assessment of hepatitis B/C medical history and risk factors
                  must be done at screening for all patients. Hepatitis B core IgM antibody (HBcIgM
                  Ab), Hepatitis B surface antigen (HBsAg) and Hepatitis C virus (HCV) Ab screen
                  (Scrn) w/Reflex testing are required at screening for all patients with a
                  positive medical history based on risk factors and/or confirmation of prior HBV
                  infection

          -  Inability to swallow or impairment of gastrointestinal function or gastrointestinal
             disease that may significantly alter the absorption of the drugs (e.g., ulcerative
             disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small
             bowel resection) that would preclude use of oral medications

          -  Major surgery =< 4 weeks prior to registration or have not recovered from side effects
             of such therapy

          -  New York Heart Association classification III or IV

          -  Patient received radiation alone previously

               -  NOTE: Radiation therapy would not be regarded as a systemic therapy

               -  EXCEPTION: Patients who have received systemic therapy followed by radiation
                  would be eligible

          -  PCNSL with systemic disease

          -  Inability to undergo or have a magnetic resonance imaging (MRI) performed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum-tolerated dose (MTD) of pomalidomide
Time Frame:Up to 28 days
Safety Issue:
Description:The MTD in this study will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description:Will be estimated by the number of patients with an objective status of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Measure:Progression-free survival (PFS)
Time Frame:From registration to progression or death due to primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL), assessed up to 4 years
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier.
Measure:Incidence of adverse events
Time Frame:Up to 12 weeks following treatment
Safety Issue:
Description:Will be assessed by CTCAE version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

February 18, 2020