Clinical Trials /

RITUXIMAB + IMMUNOTHERAPY IN FOLLICULAR LYMPHOMA

NCT03636503

Description:

This research study is studying several new investigational drug combinations as a possible treatment for follicular lymphoma. The drugs involved are: - Rituximab - Utomilumab - Avelumab

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: RITUXIMAB + IMMUNOTHERAPY IN FOLLICULAR LYMPHOMA
  • Official Title: A Multi-Cohort Phase 1b Clinical Trial of Rituximab in Combination With Immunotherapy in Untreated and Previously Treated Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 18-311
  • NCT ID: NCT03636503

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
RituximabRituximab +Utomilumab+Avelumab
UtomilumabRituximab +Utomilumab+Avelumab
AvelumabRituximab +Utomilumab+Avelumab
PF04518600Rituximab+Avelumab+PF04518600

Purpose

This research study is studying several new investigational drug combinations as a possible treatment for follicular lymphoma. The drugs involved are: - Rituximab - Utomilumab - Avelumab

Detailed Description

      This research study is a Phase 1 clinical trial. Phase 1 clinical trials test the safety of
      an investigational intervention and also try to define the appropriate dose of the
      investigational intervention to use for further studies. "Investigational" means that the
      intervention is being studied.

      Utomilumab and avelumab are drugs which may stimulate the immune system against tumor cells.
      Because they activate the immune system, they are sometimes called immunotherapy drugs. The
      FDA (the U.S. Food and Drug Administration) has not approved utomilumab or avelumab for
      treatment of this cancer.

      Rituximab is approved by the FDA (the U.S. Food and Drug Administration) as a treatment
      option for this disease.

      The purpose of this research is to learn about the effects of combining the immunotherapy
      drugs utomilumab and avelumab with rituximab in follicular lymphoma. The investigators hope
      to learn how safe the combinations of treatments are for participants with follicular
      lymphoma.
    

Trial Arms

NameTypeDescriptionInterventions
Rituximab +Utomilumab+AvelumabExperimentalRituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only Utomilumab is administered intravenously over 1 hour once every 4 weeks Avelumab is administered intravenously over 1 hour once every 2 weeks
  • Rituximab
  • Utomilumab
  • Avelumab
Rituximab+Utomilumab+PF04518600ExperimentalRituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only Utomilumab is administered intravenously over 1 hour once every 4 weeks PF-04518600 is administered intravenously over 1 hour on day 1 and day 15
  • Rituximab
  • Utomilumab
  • PF04518600
Rituximab+Avelumab+PF04518600ExperimentalRituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only Avelumab is administered intravenously over 1 hour once every 2 weeks PF-04518600 is administered intravenously over 1 hour on day 1 and day 15
  • Rituximab
  • Avelumab
  • PF04518600

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically determined follicular lymphoma, grade 1-3A, with
             pathologic review at the participating institutions, that has either:

               -  Relapsed or primary refractory after at least one line of therapy including
                  anti-CD-20 monoclonal antibody treatment (part A) or;

               -  Has had no previous anti-lymphoma therapy other than corticosteroids or
                  radiotherapy (part B).

          -  Patients with active histologic transformation are excluded. Relapsed/refractory
             patients with prior transformation may be included as long as there is no evidence of
             transformation at the time of study entry by pathology, imaging, or clinical status

          -  Patients in part B, without prior anti-lymphoma therapy, must be in need of treatment
             as defined by any of the following criteria:

               -  Symptomatic adenopathy

               -  Organ function impairment due to disease involvement, including cytopenias due to
                  marrow involvement (WBC <1.5x109/L; absolute neutrophil count [ANC] <1.0x109/L,
                  Hgb <10g/dL; platelets <100x109/L)

               -  Constitutional symptoms

               -  Maximum diameter of disease > 7cm

                  -->3 nodal sites of involvement

               -  Risk of local compressive symptoms

               -  Splenomegaly (craniocaudal diameter > 16cm on CT imaging)

               -  Clinically significant pleural or peritoneal effusion

               -  Leukemic phase (>5x109/L circulating malignant cells)

               -  Rapid generalized disease progression

               -  Renal infiltration

               -  Bone lesions

          -  Patients may have had a prior autologous stem cell transplant and may have been
             treated with autologous chimeric antigen receptor T-cells (CAR T-cells).

          -  Not in need of urgent cytoreductive therapy in the opinion of the investigator

          -  Measurable disease that has not been previously irradiated on CT scans of at least 1.5
             cm, OR if the patient has had previous radiation to the marker lesion(s), there must
             be evidence of progression since the radiation. Imaging must be completed no greater
             than 6 weeks prior to study enrollment.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see Appendix A)

          -  Adequate hematologic and organ function:

               -  Absolute neutrophil count > 1.0x109/L unless due to marrow involvement by
                  lymphoma in which case ANC must be >0.5x109/L

               -  Platelets > 75 x109/L, unless due to marrow involvement by lymphoma, in which
                  case platelets must be >50 x109/L

               -  Creatinine < 1.5 x ULN (upper limit of normal) or estimated GFR > 40ml/min

               -  Total bilirubin < 1.5 X ULN, unless Gilbert syndrome, in which case direct
                  bilirubin must be < 3 x ULN

          -  AST/ALT < 2.5 X ULN, unless documented liver involvement by lymphoma, in which case
             AST/ALT must be <5 x ULN

          -  Age >18 years

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

          -  Willingness to provide pre-treatment (or recent archival w/o intervening therapy), and
             on-treatment tumor samples by core needle or excisional surgical biopsy

        Exclusion Criteria:

          -  Patients currently receiving anticancer therapies or who have received anticancer
             therapies within 28 days of the start of study drug (including chemotherapy, radiation
             therapy, antibody based therapy, etc.), or 56 days for radioimmunotherapy. Steroids
             for symptom palliation are allowed, but must be either discontinued or on stable doses
             of < 10mg daily of prednisone (or the equivalent) at the time of initiation of
             protocol therapy.

          -  Patients may not be receiving any other investigational agents, or have received
             investigational agents within 4 weeks (or 3 half-lives, whichever is longer) of
             beginning treatment.

          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
             unless in consultation with an allergy specialist they are deemed eligible for
             retreatment with desensitization.

          -  Patients who have previously received therapy with any drug that works by a similar
             mechanism of action as any drug being tested in a given cohort will be excluded from
             that cohort but will be allowed to enroll in other open cohorts.

          -  Patients who have undergone prior allogeneic stem cell transplantation

          -  Patients with a history of or active autoimmune disease (except controlled asthma,
             Hashimoto thyroiditis, atopic dermatitis, and/or vitiligo), or requiring systemic
             corticosteroids at a dose of 10mg prednisone equivalent daily. Patients with a history
             of autoimmune disease who never required corticosteroids and with no evidence of
             disease activity, and in whom the risk of reactivation is felt not to be serious, may
             be enrolled after discussion with the overall study chair. Exceptions to this are
             patients with a history of inflammatory bowel disease (ulcerative colitis and Crohn's
             disease). These patients are excluded regardless of whether their disease is active or
             inactive.

          -  Patients with active pneumonitis or colitis, or patients with chronic liver disease
             and/or cirrhosis

          -  Patients, who have had a major surgery or significant traumatic injury within 4 weeks
             of start of study drug, patients who have not recovered from the side effects of any
             major surgery (defined as requiring general anesthesia) or patients that may require
             major surgery during the course of the study.

          -  Patients with known leptomeningeal or brain metastases. Imaging or spinal fluid
             analysis to exclude CNS involvement is not required, unless there is clinical
             suspicion by the treating investigator.

          -  Patients with known HIV infection or hepatitis B or C infection. Testing for HIV is
             optional. Testing for hepatitis B and C is mandatory. Patients with hepatitis B core
             Ab positivity but negative surface antigen and negative viral load may be enrolled if
             they can be treated with a prophylactic agent (eg, entecavir); patients with hepatitis
             C seropositivity who have undergone successful treatment with negative viral load can
             also be enrolled.

          -  Patients with a systemic fungal, bacterial, viral, or other infection not controlled
             (defined as exhibiting ongoing signs/symptoms related to the infection and without
             improvement, despite appropriate antibiotics or other treatment).

          -  Prior history of another malignancy (except for non-melanoma skin cancer or in situ
             cervical or breast cancer) unless disease free for at least three years. Patients with
             prostate cancer are allowed if PSA is less than 1.

          -  Patients should not have received immunization with attenuated live vaccine within one
             week of study entry or during study period.

          -  Female patients who are pregnant or breast feeding, or adults of reproductive
             potential who are not using effective birth control methods. Women of child bearing
             potential (WOCBP) or male study participants of reproductive potential must agree to
             use double barrier birth control method of contraception during the course of the
             study treatment period and for 3 months after completing study treatment. WOCBP are
             defined as sexually mature women who have not undergone a hysterectomy or who are not
             postmenopausal (no menses) for at least 12 consecutive months. WOCBP must have a
             negative urine or serum pregnancy test within 14 days prior to administration of
             treatment.

          -  History of noncompliance to medical regimens.

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as:

               -  New York Heart Association Class III or IV cardiac disease, including
                  pre-existing clinically significant arrhythmia, congestive heart failure, or
                  cardiomyopathy

               -  Patients with a history of previous anthracycline treatment and are at risk of
                  cardiac failure (New York Heart Association Class II or above) are excluded from
                  cohorts A2, A3, and B2 (cohorts that include PF04518600)

               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction within 6 months of start of study drug, serious uncontrolled cardiac
                  arrhythmia or any other clinically significant cardiac disease

          -  Patients with any one of the following currently on or in the previous 6 months will
             be excluded from cohorts A2, A3, and B2 (any cohort that includes treatment with
             PF04518600) myocardial infarction, congenital long QT syndrome, torsade's de points,
             left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral
             artery bypass graft, cerebrovascular accident, transient ischemic attack or
             symptomatic pulmonary embolism or other clinically significant episode of
             thrombo-embolic disease*. Ongoing cardiac dysrhythmias of NCI CTCAE grade > 2, atrial
             fibrillation of any grade, or QTcF interval >470msec at screening (except in case of
             right bundle branch block, these cases must be discussed with the principal
             investigator). *Cases must be discussed in detail with the principal investigator to
             judge eligibility. Anticoagulation (heparin only, no vitamin K antagonists or factor
             Xa inhibitors will be allowed if indicated.

          -  Other uncontrolled intercurrent illness that would limit adherence to study
             requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended phase 2 dosing
Time Frame:2 years
Safety Issue:
Description:Lugano criteria

Secondary Outcome Measures

Measure:Partial Response Rate
Time Frame:2 years
Safety Issue:
Description:Lugano criteria
Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:Lugano criteria
Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:Lyric criteria
Measure:Stable disease rate
Time Frame:2 years
Safety Issue:
Description:Lugano criteria
Measure:Stable disease rate
Time Frame:2 years
Safety Issue:
Description:Lyric criteria
Measure:Progressive disease rate
Time Frame:2 years
Safety Issue:
Description:Lyric criteria
Measure:Progressive disease rate
Time Frame:2 years
Safety Issue:
Description:Lugano criteria
Measure:Complete response rate
Time Frame:2 years
Safety Issue:
Description:Lyric criteria
Measure:Progression FreeSurvival
Time Frame:2 years
Safety Issue:
Description:Lugano criteria
Measure:Progression FreeSurvival
Time Frame:2 years
Safety Issue:
Description:Lyric criteria
Measure:Overall Survival Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to Next Treatment Response Duration
Time Frame:2 years
Safety Issue:
Description:
Measure:Rate of Grade 3 and higher toxicities
Time Frame:2 years
Safety Issue:
Description:Regardless of attribution
Measure:Rate of Grade 3 and higher toxicities
Time Frame:2 years
Safety Issue:
Description:Related to study treatment
Measure:Rate of Grade 2 or higher toxicity
Time Frame:2 years
Safety Issue:
Description:Related to study treatment
Measure:Rate of Adverse events leading to discontinuation due to toxicity
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Lymphoma

Last Updated

November 15, 2019