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

Overview

About this study

The purpose of this study is to determine the safety and tolerability of weekly intravenous (IV) administration of XmAb13676 and to determine the maximally tolerated dose (MTD) after the first dose, and then to determine the MTD after second and subsequent infusions.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Main Patient Inclusion Criteria for All Cohorts or As Specified:

  • Able to provide written informed consent.
  • Adult (age ≥ 18 years).
  • Diagnosis of either:
    • Non-CLL B-cell malignancy, including (but not limited to) low-grade and/or follicular NHL, diffuse large B-cell lymphoma, transformed lymphoma, Burkitt’s or other high-grade lymphoma, mantle cell lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma, hairy cell leukemia, and Waldenström macroglobulinemia; or
    • CLL/SLL (including Richter transformation).
  • Patient must be ineligible for or have exhausted standard therapeutic options and have relapsed or refractory disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Female patients and male patients with female partners of childbearing potential must agree to use a highly effective method of birth control during the study and for 60 days after last dose of XmAb13676.  A woman is considered of childbearing potential (WOCBP); i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy (CTFG, 2014).  WOCBP must have a negative urine pregnancy test during screening and at Day 1 of each cycle prior to study drug infusion and must use a highly effective method of birth control during the study and for 60 days following last dose of XmAb13676.
  • Able and willing to complete the entire study according to the study schedule.

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

  • Histologically confirmed diagnosis of DLBCL or transformed low-grade lymphoma with measurable disease.
  • Based on the 2016 World Health Organization classification, patients must have one of the following diagnoses to be eligible: DLBCL, not otherwise specified (NOS); T-cell/histiocyte-rich large B-cell lymphoma; primary mediastinal (thymic) large B-cell lymphoma; intravascular large B-cell lymphoma; primary cutaneous DLBCL leg type; EBV+ DLBCL, NOS; DLBCL associated with chronic inflammation; high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements; high-grade B-cell lymphoma, NOS; Grade 3b follicular lymphoma; or transformed follicular lymphoma.
  • 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. Patients with transformed follicular lymphoma must have relapsed/refractory disease after a total of 2 or more prior lines of chemoimmunotherapy (at least one of which must have been directed at the transformed DLBCL).
  • Transformed lymphoma (DLBCL) arising from CLL/SLL is not eligible for this expansion cohort but rather is being studied in the Richter transformation cohort.
  • Not a candidate for or refusing treatment with hematopoietic stem cell transplantation.

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

  • Diagnosis of follicular lymphoma Grades 1-3a.
  • Patient must be ineligible for or have exhausted standard therapeutic options and have had 2 or more prior systemic regimens.
  • Transformed follicular lymphoma (DLBCL) is not eligible for this cohort but is rather being studied in the DLBCL cohort.

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

  • Diagnosis of mantle cell lymphoma.
  • 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)

  • Diagnosis of Waldenström macroglobulinemia.
  • 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)

  • Diagnosis of Richter transformation.

Additional Patient Inclusion Criteria for Other Indolent Lymphomas Cohort (Expansion Phase)

  • 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.
  • 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, except CLL patients who are receiving ibrutinib or acalabrutinib therapy may continue to receive the drug up until the day before treatment with XmAb13676, but may not continue therapy with those drugs once XmAb13676 treatment has begun.
  • Prior solid organ transplantation.
  • Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to malignant bone marrow involvement).
  • Diagnosis of multiple myeloma/plasma cell leukemia or B-cell acute lymphoblastic leukemia.
  • Known intolerance to CD20 monoclonal antibody therapy.
  • History of primary central nervous system (CNS) lymphoma or CNS neoplastic disease.
  • Platelet count <50 x 10^9/L.
  • Absolute neutrophil count < 1.0 x 10^9/L.
  • AST at screening > 3x upper limit of normal (ULN).
  • ALT at screening > 3 x ULN.
  • Bilirubin > 1.5 mg/dL (unless prior diagnosis and documentation of ongoing hemolysis or Gilbert's syndrome has been made).
  • Estimated creatinine clearance < 40 mL/minute calculated by the Cockcroft-Gault or MDRD (Levey, 1999) formulas at screening.
  • Active (requiring immunosuppressive medications) or uncontrolled autoimmune disease.
  • Clinically significant cardiac or cardiovascular disease, such as CHF (e.g., NYHA class III-IV), MI or unstable angina within 6 months prior to study entry, or uncontrolled cardiac arrhythmias.
  • Clinically significant pulmonary compromise, including but not limited to a supplemental oxygen requirement.
  • Seizure disorder.
  • History of stroke within the past 6 months prior to study entry.
  • History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy, that in the opinion of the Investigator would pose a risk to 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 hepatitis B surface antigen (HBsAg), or positive test for hepatitis B core antibody (HBcAb; unless serology is positive due to recent intravenous immunoglobulin therapy). HBcAb positivity will be allowed if one or more of the following is true:
    • HBsAb is present; or
    • hepatitis B DNA testing is negative and the patient is receiving hepatitis B reactivation prophylaxis with entecavir, tenofovir, or lamivudine.
  • Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the End of Study (EOS) visit
  • Positive urine pregnancy test (i.e., urine human chorionic gonadotropin) at screening.
  • Patients with SLL are excluded from Part C dose escalation.
  • Live viral vaccine within 2 weeks of the first dose XmAb13676.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Asher Alban Chanan Khan, M.B.B.S., M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20401445

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