Clinical Trials /

Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

NCT02568553

Description:

This phase I trial studies the side effects and best dose of lenalidomide and blinatumomab when given together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement. Biological therapies, such as lenalidomide and blinatumomab, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

Related Conditions:
  • Burkitt Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Mediastinal B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Mediastinal Lymphoma
  • Non-Hodgkin Lymphoma
  • Small Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma
  • Official Title: A Phase I Trial of the Combination of Lenalidomide and Blinatumomab in Patients With Relapsed or Refractory Non-Hodgkins Lymphoma (NHL)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-01640
  • SECONDARY ID: NCI-2015-01640
  • SECONDARY ID: PHI-79
  • SECONDARY ID: 9924
  • SECONDARY ID: 9924
  • SECONDARY ID: UM1CA186644
  • SECONDARY ID: UM1CA186717
  • NCT ID: NCT02568553

Conditions

  • CD19 Positive
  • Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
  • Recurrent Burkitt Lymphoma
  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mediastinal Lymphoma
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
  • Refractory Burkitt Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Follicular Lymphoma
  • Refractory Mantle Cell Lymphoma
  • Refractory Marginal Zone Lymphoma
  • Refractory Mediastinal Lymphoma
  • Refractory Non-Hodgkin Lymphoma
  • Refractory Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Treatment (blinatumomab, lenalidomide)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (blinatumomab, lenalidomide)

Purpose

This phase I trial studies the side effects and best dose of lenalidomide and blinatumomab when given together in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement. Biological therapies, such as lenalidomide and blinatumomab, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of lenalidomide when given in combination
      with blinatumomab in the proposed regimen.

      SECONDARY OBJECTIVES:

      I. To observe and record anti-tumor activity anti-tumor response (complete response [CR] and
      partial response [PR] as per International workshop lymphoma response criteria).

      II. To investigate the immune response to blinatumomab alone and in combination with
      lenalidomide.

      III. To document the infection rate with a 96-hour bag change schedule for blinatumomab.

      OUTLINE: This is a dose-escalation study of lenalidomide.

      INDUCTION: Patients receive blinatumomab intravenously (IV) continuously on days 1-56 and
      lenalidomide orally (PO) on days 29-49 in the absence of disease progression or unacceptable
      toxicity.

      CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV
      continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days
      for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

      MAINTENANCE: Patients receiving response including stable disease after completion of
      Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2
      years in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (blinatumomab, lenalidomide)ExperimentalINDUCTION: Patients receive blinatumomab IV continuously on days 1-56 and lenalidomide PO on days 29-49 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving response including stable disease receive blinatumomab IV continuously on days 1-7 and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receiving response including stable disease after completion of Consolidation receive lenalidomide PO on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Blinatumomab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed relapsed cluster of differentiation (CD)19+
             non-Hodgkin lymphoma (NHL) (included in this category are follicular grade I, II, III,
             marginal zone, mantle cell, gray zone, primary mediastinal, Burkitt's, diffuse large B
             cell, small lymphocytic lymphoma); patients previously treated with CD19-targeted
             therapy (including chimeric antigen receptor T-cells [CAR T]) must have a subsequent
             biopsy and/or flow cytometry confirming CD19 positivity

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Life expectancy of greater than 12 weeks

          -  Absolute neutrophil count > 1000/mcL

          -  Platelets >= 50,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  AST (SGOT)/ALT(SGPT) (only if elevated liver function tests [LFTs] are due to disease)
             =< 5.0 x institutional upper limit of normal

          -  Body surface area (BSA)-normalized creatinine clearance >= 60 mL/min/1.73 m^2 (using
             Cockcroft-Gault creatinine clearance [CrCl])

          -  Patients must have had at least two prior chemotherapeutic or biologic (e.g. rituximab
             alone) regimens and not currently eligible for standard curative options; steroids
             alone and local radiation do not count as regimens; radiation to > 1 site and
             transplant are considered prior regimens

          -  Any prior therapy must have been completed at least 4 weeks prior to entry into the
             study

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again
             within 24 hours of starting lenalidomide and must either commit to continued
             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 lenalidomide; FCBP must also agree to
             ongoing pregnancy testing; men must agree to use a latex condom during sexual contact
             with a FCBP even if they have had a successful vasectomy; all patients must be
             counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal
             exposure

          -  Patients must have radiographically measurable disease defined as at least one lesion
             that can be accurately measured in at least one dimension (longest diameter to be
             recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed
             tomography (CT) scan; lesions in previously irradiated anatomic areas (external beam
             radiation) cannot be considered target lesions unless there has been documented growth
             of those lesions after radiotherapy

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Human immunodeficiency virus (HIV) infected patients are eligible provided they meet
             all the other eligibility criteria of the study in addition to the following:

               -  No history of acquired immune deficiency syndrome (AIDS)-defining conditions
                  other than lymphoma or history of CD4+ T-cells below 200/mm^3 prior to beginning
                  combination antiretroviral therapy (cART)

               -  After HIV diagnosis and during treatment with cART, patients should have
                  maintained CD4+ T-cells >= 350/mm^3 prior to lymphoma diagnosis; patients who
                  never immune reconstituted to a stable level above 350/mm^3 are not eligible

               -  At time of study entry CD4+ T-cells must have recovered from prior lymphoma
                  therapy to >= 250/mm^3

               -  At the time of study entry the HIV viral load must be undetectable by standard
                  laboratory assay

               -  During prior lymphoma therapy, patients must not have experienced documented
                  infections attributed to the HIV+ status

               -  No history of non-adherence to cART and willing to adhere to cART while on study

               -  Antiretroviral drugs with overlapping or similar toxicity profiles as study
                  agents not allowed:

                    -  Efavirenz not allowed due to potential central nervous system (CNS) toxicity

                    -  Stavudine not allowed due to potential neuropathic effects

                    -  Zidovudine not allowed due to myelosuppressive effects

               -  Patients must be willing to be followed at a minimum of approximately every 3
                  months by physician expert in HIV disease management

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
             the study or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier

          -  Patients who are receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to lenalidomide and blinatumomab or other agents used in study

          -  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

          -  Pregnant women are excluded from this study because lenalidomide is an agent with the
             potential for teratogenic or abortifacient effects; because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with lenalidomide, breastfeeding should be discontinued if the mother is
             treated with lenalidomide

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known active hepatitis, type B or C; patients on suppressive therapy with a negative
             viral load and no evidence of hepatic damage are eligible

          -  Prior treatment with blinatumomab or CD-directed CAR T-cell therapy

          -  Prior treatment with lenalidomide within 8 weeks prior to entering the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of toxicity
Time Frame:Up to 24 months
Safety Issue:
Description:Will be graded as according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018). Toxicities (grade, type, cycle, and attribution) experienced will be listed for each patient and summarized using standard descriptive methods.

Secondary Outcome Measures

Measure:Clinical anti-tumor response (complete response and partial response as per International workshop lymphoma response criteria)
Time Frame:Up to 24 months
Safety Issue:
Description:Will be summarized using standard descriptive methods.
Measure:Changes in the frequency of CD4+ T cells
Time Frame:Baseline to up to day 57
Safety Issue:
Description:Will be assessed and compared at each time point, using regression methods that incorporate repeated measures. For each of the first 2 CD4+ measures, will compare the day 0 values (prior to any treatment) to the day 15 values (after 2 weeks of blinatumomab) and the day 57 (after 4 weeks of the both blinatumomab and lenalidomide) to the day 15 value. Additional analysis, will be undertaken to explore the relationship between changes (or lack of changes) and response. The paired-sample t-test will be used to provide a sense of the power/sensitivity that will be available for these comparisons.
Measure:Changes in the production of interferon (INF)-gamma from CD4+ T cells
Time Frame:Baseline to up to day 57
Safety Issue:
Description:Will be assessed and compared at each time point, using regression methods that incorporate repeated measures. For each of the first CD8+ T-cell frequencies and INF-gamma production, will compare the day 0 values (prior to any treatment) to the day 15 values (after 2 weeks of blinatumomab) and the day 57 (after 4 weeks of the both blinatumomab and lenalidomide) to the day 15 value. Additional analysis, will be undertaken to explore the relationship between changes (or lack of changes) and response. The paired-sample t-test will be used to provide a sense of the power/sensitivity that will be available for these comparisons.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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