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Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma

NCT04512716

Description:

This is a single-cohort pilot study; patients will receive 131-I apamistamab 75 mCi prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I apamistamab.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • B-Cell Lymphoblastic Lymphoma
  • Chronic Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Richter Syndrome
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
  • Official Title: Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 20-382
  • NCT ID: NCT04512716

Conditions

  • B-ALL
  • DLBCL
  • B ALL
  • Dlbcl-Ci
  • DLBCL Unclassifiable
  • DLBCL, Nos Genetic Subtypes
  • DLBCL Activated B-Cell Type
  • DLBCL Germinal Center B-Cell Type
  • Diffuse Large B-cell Lymphoma
  • HGBL
  • HGBL, Nos

Interventions

DrugSynonymsArms
131-I ApamistamabIomab-BB-Cell Acute Lymphoblastic Leukemia/Diffuse Large B-Cell Lym
CAR T-cellB-Cell Acute Lymphoblastic Leukemia/Diffuse Large B-Cell Lym

Purpose

This is a single-cohort pilot study; patients will receive 131-I apamistamab 75 mCi prior to CAR T-cell infusion in order to determine the maximum tolerated dose of 131-I apamistamab.

Trial Arms

NameTypeDescriptionInterventions
B-Cell Acute Lymphoblastic Leukemia/Diffuse Large B-Cell LymExperimentalParticipants will have relapsed or refractory B-Cell Acute Lymphoblastic Leukemia or Diffused Large B-Cell Lymphoma
  • 131-I Apamistamab
  • CAR T-cell

Eligibility Criteria

        Patients with B-ALL or DLBCL (or subtypes thereof) who have relapsed or refractory disease
        will be eligible. Refractory disease is defined by failure to achieve at least a partial
        response or disease progression within 6 months of the last therapy. Patients who initially
        respond but subsequently demonstrate disease progression are considered to have relapsed
        disease

        Participant Inclusion Criteria:

        - To be eligible for leukapheresis, patients must have a CD19+ B-cell malignancy with
        relapsed or refractory disease, defined below. To be eligible for 131-I apamistamab
        conditioning and treatment with 19-28z CAR T-cells, patients must additionally have
        detectable evidence of residual malignancy at the time of assessment prior to CAR T-cell
        infusion (as defined below), regardless of therapy administered following leukapheresis.

        a. Patients with diffuse large B-cell lymphoma (de novo or DLBCL transformed from an
        indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia [Richter syndrome]) or
        high-grade B-cell lymphoma (HGBL): ("DLBCL patients") i. Defined as relapsed or refractory
        DLBCL or high-grade B-cell lymphoma (HGBL) following 2 or more prior chemoimmunotherapy
        regimens (with at least one course including an anthracycline and CD20-directed therapy)
        following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma, and
        requiring further treatment.

        ii. Patients must have at least one FDG-avid (PET-avid) measurable lesion iii. Biopsy
        confirmation of relapsed of refractory DLBCL is required b. Patients with B-cell acute
        lymphoblastic leukemia or B lymphoblastic lymphoma (ALL) or chronic myeloid leukemia (CML)
        in lymphoid blast crisis: ("B-ALL patients") i. Patients with Philadelphia
        chromosome-negative B-cell ALL must have been refractory to at least 1 line of multi-agent
        chemotherapy or relapsed following at least 1 prior multiagent systemic chemotherapy
        regimen that included induction and consolidation therapy ii. Patients with Philadelphia
        chromosome-positive ALL or CML in lymphoid blast crisis must have exhibited persistent
        disease following therapy with a second- or third-generation tyrosine kinase inhibitor iii.
        Patients must have ≥5% bone marrow involvement and/or at least one FDG-avid (PET-avid)
        measurable extramedullary lesion

          -  While prior CD19-targeted therapies, including CAR T-cell therapy, do not exclude
             participation, CD19 expression by immunohistochemical staining or flow cytometry must
             be confirmed prior to enrollment.

          -  Age ≥ 18 years of age

          -  Creatinine clearance ≥50 mL/min as calculated by the Cockroft-Gault formula

          -  Direct bilirubin ≤2.0 mg/dL, AST and ALT ≤3.0x upper limit of normal (ULN), unless
             liver dysfunction is thought to be related to underlying malignancy

          -  Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse
             oximetry.

          -  Adequate bone marrow function meeting the following criteria as defined below, without
             requiring blood product or granulocyte-colony stimulating factor support in the past 7
             days, unless cytopenias are attributed to underlying malignancy in the opinion of the
             investigator:

               1. Absolute neutrophil count ≥0.5k/µL,

               2. Platelets ≥30k/µL,

               3. Hemoglobin ≥7g/dL.

          -  ECOG performance status 0-2.

        Participant Exclusion Criteria:

          -  ECOG performance status ≥3.

          -  Pregnant or lactating patients. Patients of childbearing age should use effective
             contraception while on this study and continue for 1 year after all treatment is
             finished.

          -  Impaired cardiac function (LVEF <40%) as assessed by echocardiogram or MUGA scan
             during screening

          -  Patients with active graft versus host disease following allogeneic hematopoietic cell
             transplantation requiring systemic T-cell suppressive therapy are ineligible

          -  Patients with active autoimmune disease requiring systemic T-cell suppressive therapy
             are ineligible

          -  Patients with following cardiac conditions will be excluded:

               1. New York Heart Association (NYHA) stage III or IV congestive heart failure

               2. Myocardial infarction ≤6 months prior to enrollment

               3. Any history of clinically significant ventricular arrhythmia or unexplained
                  syncope, not believed to be vasovagal in nature or due to dehydration

               4. Any history of severe non-ischemic cardiomyopathy with LVEF ≤20%

          -  Have current or prior positive test results for human immunodeficiency virus (HIV) or
             hepatitis B (HBV) or C (HCV), with the following exceptions:

               1. Subjects who have positive HBV test results due to having been previously
                  vaccinated against hepatitis B, as evidenced by negative hepatitis B surface
                  antigen (HBsAg), negative anti- hepatitis B core protein (HBc) and positive
                  antibody to the HBsAg (anti-HBs) are not excluded.

               2. Subjects who have antibodies to HCV or who have hepatitis B core antibody, with
                  undetectable viremia by PCR, and with adequate organ function as defined in the
                  protocol, are not excluded.

          -  Patients with uncontrolled systemic fungal, bacterial, viral or other infection are
             ineligible.

          -  Patients with any concurrent active malignancies as defined by malignancies requiring
             any therapy other than expectant observation or hormonal therapy, with the exception
             of squamous and basal cell carcinoma of skin.

          -  Patients with history or presence of clinically significant neurological disorders
             such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible.

          -  Any other issue which, in the opinion of the treating physician, would make the
             patient ineligible for the study.

          -  Patients with circulating human anti-mouse antibodies to BC8 noted on initial
             screening (see Appendix III)

        Subject Inclusion Criteria for 131-I Apamistamab Infusion Patients should meet performance
        status and organ function parameters as specified in Section 6.1, without known development
        of an exclusion criterion in Section 6.2, prior to proceeding to 131-I apamistamab
        infusion. See Section 9.2 re: screening for treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicities and maximum tolerated dose of 131-I apamistamab, when given in combination with 19-28z CAR T-cells for treatment of relapsed or refractory B-cell ALL or DLBCL
Time Frame:30 days after treatment
Safety Issue:
Description:To determine the safety and tolerability of a single 75 mCi dose of 131-I apamistamab given prior to 19-28z CAR T-cell infusion in patients with relapsed or refractory B-cell ALL or DLBCL.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • CD19+ B-cell malignancy
  • 131-I apamistamab
  • B-cell malignancy
  • Memorial Sloan Kettering Cancer Center

Last Updated

March 16, 2021