Clinical Trials /

Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies

NCT02924402

Description:

The purpose of this study is to determine the safety and tolerability of intravenous (IV) administration of XmAb13676 and to determine the maximally tolerated dose (MTD) and/or recommended dose (RD).

Related Conditions:
  • B-Cell Neoplasm
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
  • Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
  • Grade 1 Follicular Lymphoma
  • Grade 2 Follicular Lymphoma
  • Grade 3 Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Nodal Marginal Zone Lymphoma
  • Richter Syndrome
  • Splenic Marginal Zone Lymphoma
  • Thymic Mucosa-Associated Lymphoid Tissue Lymphoma
  • Transformed Non-Hodgkin Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate Safety and Tolerability of XmAb13676 in Patients With CD20-expressing Hematologic Malignancies
  • Official Title: A Phase 1 Multidose Study to Evaluate the Safety and Tolerability of XmAb13676 in Patients With CD20-Expressing Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: XmAb13676-01
  • NCT ID: NCT02924402

Conditions

  • B-cell Non-Hodgkins Lymphoma
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
XmAb13676CLL/SLL (Group CLL)

Purpose

The purpose of this study is to determine the safety and tolerability of intravenous (IV) administration of XmAb13676 and to determine the maximally tolerated dose (MTD) and/or recommended dose (RD).

Trial Arms

NameTypeDescriptionInterventions
Non-CLL B Cell Malignancies (Group NHL)ExperimentalXmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
  • XmAb13676
CLL/SLL (Group CLL)ExperimentalXmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
  • XmAb13676

Eligibility Criteria

        Inclusion Criteria:

          -  Able to provide written informed consent

          -  Diagnosis of either Non-CLL B cell malignancy or CLL/SLL

          -  Ineligible for or have exhausted standard therapeutic options and have relapsed or
             refractory disease

          -  ECOG performance status 0-2

          -  Fertile patients must agree to use highly effective contraception during and for 4
             weeks after last dose of XmAb13676

          -  Able and willing to complete the entire study

        Additional Patient Inclusion Criteria for the DLBCL Cohort (Expansion Phase)

          1. Histologically confirmed diagnosis (specified by 2016 World Health Organization) of
             DLBCL or transformed low-grade lymphoma with measurable disease

          2. Patient must be refractory or have relapsed after 2 or more standard therapeutic
             options, at least one of which must have included anti-CD20 antibody therapy.

          3. Not a candidate for or refusing treatment with hematopoietic stem cell transplantation

        Additional Patient Inclusion Criteria for the Follicular Lymphoma Cohort (Expansion Phase)

          1. Diagnosis of follicular lymphoma Grades 1-3a

          2. Patient must be ineligible for or have exhausted standard therapeutic options and have
             had 2 or more prior systemic regimens.

        Additional Patient Inclusion Criteria for the Mantle Cell Lymphoma Cohort (Expansion Phase)

          1. Diagnosis of mantle cell lymphoma

          2. Patient must be ineligible for or have exhausted standard therapeutic options and have
             had 2 or more prior systemic regimens.

        Additional Patient Inclusion Criteria for the Waldenström Macroglobulinemia Cohort
        (Expansion Phase)

          1. Diagnosis of Waldenström macroglobulinemia

          2. Patient must be ineligible for or have exhausted standard therapeutic options and have
             had 2 or more prior systemic regimens.

        Additional Patient Inclusion Criteria for Richter Transformation Cohort (Expansion Phase)

        1. Diagnosis of Richter transformation Additional Patient Inclusion Criteria for Other
        Indolent Lymphomas Cohort (Expansion Phase)

          1. Diagnosis of other indolent B-cell, non-Hodgkin's lymphomas, specifically the
             following: MALT lymphoma, nodal marginal zone lymphoma, and splenic marginal zone
             lymphoma (NOTE: SLL is not eligible)

          2. Patient must be ineligible for or have exhausted standard therapeutic options and have
             had 2 or more prior systemic regimens.

        Exclusion Criteria:

          -  Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20
             antibodies within 4 weeks, or small molecule or investigational agents within 6
             elimination half-lives of the first dose of XmAb13676

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Failure to recover from Grade 3 or 4 toxicity from previous treatment

          -  Multiple myeloma/plasma cell leukemia or B cell acute lymphoblastic leukemia

          -  Known intolerance to CD20 monoclonal antibody therapy

          -  History of primary central nervous system lymphoma or neoplastic central nervous
             system disease

          -  Platelet count < 50 x 10^9/L

          -  Absolute neutrophil count < 1.0 x 10^9/L

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at screening > 3x
             upper limit of normal (ULN)

          -  Bilirubin > 1.5 mg/dL unless prior diagnosis and documentation of ongoing hemolysis or
             Gilbert's syndrome has been made)

          -  Estimated creatinine clearance < 50 40 mL/min

          -  Active/uncontrolled autoimmune disease

          -  Clinically significant cardiac/cardiovascular disease, or pulmonary compromise

          -  Seizure disorder

          -  History of stroke with the past year6 mos prior to study entry

          -  History or evidence of a clinically unstable/uncontrollable disorder, condition or
             disease other than primary malignancy, that in the opinion of the Investigator would
             pose a risk to the patient safety or interfere with the study evaluation, procedures
             or completion

          -  Evidence of any serious bacterial, viral, parasitic or systemic fungal infections
             within the 30 days prior to study entry

          -  Positive test for human immunodeficiency virus (HIV) or hepatitis C (HCV) antibodies
             (unless HCV viral load test by PCR is negative)

          -  Positive test for HbsAg, or positive test for HBcAb (unless serology is positive due
             to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if
             HBsAb is present.

          -  Patient is pregnant or breast feeding, or planning to become pregnant while enrolled
             in the study, up to the End of Study visit

          -  Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as determined by the number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:Baseline Day 1 through Day 56
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Xencor, Inc.

Trial Keywords

  • NHL
  • B-cell Prolymphocytic Leukemia
  • Transformed Lymphoma
  • Burkitt's Lymphoma
  • Mantle Cell Lymphoma
  • Hairy Cell Leukemia
  • Splenic Marginal Zone Lymphoma
  • Waldenstrom's Macroglobulinemia
  • Variant Hairy Cell Leukemia
  • Splenic B-cell Lymphoma/Leukemia
  • Lymphoplasmacytic Lymphoma
  • Extranodal Marginal Zone Lymphoma (MALT)
  • MALT Lymphoma
  • Nodal Marginal Zone Lymphoma
  • Follicular Lymphoma
  • In Situ Follicular Neoplasia
  • Duodenal-type Follicular Lymphoma
  • Large B-cell Lymphoma with IRF4 rearrangement
  • Primary Cutaneous Follicle Center Lymphoma
  • Diffuse Large B-cell Lymphoma
  • DLBCL
  • T-cell/Histiocyte-Rich Large B-cell Lymphoma
  • Primary Cutaneous DLBCL, leg type
  • EBV-positive DLBCL, NOS
  • EBV-positive Mucocutaneous Ulcer
  • DLBCL Associated with Chronic Inflammation
  • Lymphomatoid Granulomatosis
  • Primary Mediastinal (Thymic) Large B-cell Lymphoma
  • Intravascular Large B-cell Lymphoma
  • ALK+ Large B-cell Lymphoma
  • Plasmablastic Lymphoma
  • Primary Effusion Lymphoma
  • HHV8+ DLBCL
  • Burkitt-like Lymphoma with 11q Aberration
  • High-grade B-cell Lymphoma
  • B-cell Lymphoma, unclassifiable
  • Post-transplant Lymphoproliferative Disorder
  • PTLD
  • CLL
  • SLL
  • High-grade Lymphoma
  • Richter's Transformation

Last Updated

September 9, 2020