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

Primary Purpose

B-cell Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
XmAb13676
Sponsored by
Xencor, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Non-Hodgkins Lymphoma focused on measuring 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, SLL, High-grade Lymphoma, Richter's Transformation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 5 months (male patients) and 8 months (female patients) 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.

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, and 8 months after the last dose of study drug
  • Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening
  • Live viral vaccine within 2 weeks of the first dose of XmAb13676

Sites / Locations

  • Moores UC San Diego Cancer Center
  • Mayo Clinic
  • Northside HospitalRecruiting
  • Northwestern University
  • The University of Chicago MedicineRecruiting
  • University of MichiganRecruiting
  • Roswell Park Cancer Center
  • Gabrail Cancer Center Research
  • The Ohio State University Wexner Medical Center and James Cancer HospitalRecruiting
  • MD Anderson Cancer CenterRecruiting
  • UVA Health System, Division of Hematology & Oncology
  • Swedish Cancer InstituteRecruiting
  • Froedtert Hospital and Medical College of WisconsinRecruiting
  • Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud OuestRecruiting
  • Hopital Henri MondorRecruiting
  • Institut Paoli Calmette Dpt of Oncology/HematologyRecruiting
  • Chu Montpellier, Hematologie Clinique St. EloiRecruiting
  • CHU de NantesRecruiting
  • Centre Antoine LacassagneRecruiting
  • CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie CellulaireRecruiting
  • Centre Hospitalier Lyon-Sud, Service d'HematologieRecruiting
  • Centre Henri BecquerelRecruiting
  • Institut Universitaire du Cancer Toulouse OncopoleRecruiting
  • CLCC Institut Gustave RoussyRecruiting
  • Inje University Busan Paik HospitalRecruiting
  • Dong A University Medical Center (Dong A University Hospital)Recruiting
  • Gachon University Gil Medical CenterRecruiting
  • Seoul National University College of Medicine, Seoul National University Bungdang HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Samsung Medical CenterRecruiting
  • The Catholic University of Korea, Seoul St. Mary's HospitalRecruiting
  • Ewha Womans University Mokdong HospitalRecruiting
  • Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation TrustRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Non-CLL B Cell Malignancies (Group NHL) Part A

CLL/SLL (Group CLL) Part A

Non-CLL B Cell Malignancies (Group NHL) Part B

CLL/SLL (Group CLL) Part B

Non-CLL B Cell Malignancies (Group NHL) Part C / Expansion

Non-CLL B Cell Malignancies (Group NHL) Part D / Expansion

Arm Description

XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

XmAb13676 administered SC up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion

Outcomes

Primary Outcome Measures

Safety and tolerability as determined by the number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb13676 dosing

Secondary Outcome Measures

Full Information

First Posted
September 14, 2016
Last Updated
February 27, 2023
Sponsor
Xencor, Inc.
Collaborators
ICON Clinical Research
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1. Study Identification

Unique Protocol Identification Number
NCT02924402
Brief Title
Study to Evaluate Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-expressing Hematologic Malignancies
Official Title
A Phase 1 Multidose Study to Evaluate the Safety and Tolerability of XmAb13676 (Plamotamab) in Patients With CD20-Expressing Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2016 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xencor, Inc.
Collaborators
ICON Clinical Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukemia
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, SLL, High-grade Lymphoma, Richter's Transformation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
This study will enroll two parallel disease groups in escalation: patients with non-CLL B cell malignancies and patients with CLL/SLL/Richter's Transformation. In expansion it will enroll DLBCL and FL
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
270 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Non-CLL B Cell Malignancies (Group NHL) Part A
Arm Type
Experimental
Arm Description
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Arm Title
CLL/SLL (Group CLL) Part A
Arm Type
Experimental
Arm Description
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Arm Title
Non-CLL B Cell Malignancies (Group NHL) Part B
Arm Type
Experimental
Arm Description
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Arm Title
CLL/SLL (Group CLL) Part B
Arm Type
Experimental
Arm Description
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Arm Title
Non-CLL B Cell Malignancies (Group NHL) Part C / Expansion
Arm Type
Experimental
Arm Description
XmAb13676 administered IV up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Arm Title
Non-CLL B Cell Malignancies (Group NHL) Part D / Expansion
Arm Type
Experimental
Arm Description
XmAb13676 administered SC up to 8 weeks, if receiving benefit, this can be extended at investigator's discretion
Intervention Type
Biological
Intervention Name(s)
XmAb13676
Intervention Description
Biological
Primary Outcome Measure Information:
Title
Safety and tolerability 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
Title
Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb13676 dosing
Time Frame
Baseline Day 1 through Day 56

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide written informed consent Diagnosis of either Non-CLL B cell malignancy 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 5 months (male patients) and 8 months (female patients) after last dose of XmAb13676 Able and willing to complete the entire study Additional Patient Inclusion Criteria for the DLBCL Cohort (Expansion Phase) Histologically confirmed diagnosis (specified by 2016 World Health Organization) of DLBCL or transformed low-grade lymphoma with measurable disease 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. 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. Exclusion Criteria: Cytotoxic chemotherapy, radiotherapy, or immunotherapy including other anti-CD20 antibodies within 4 weeks, or small molecule or investigational agents within 5 elimination half-lives of the first dose of XmAb13676 Prior 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 < 40 mL/min Active/uncontrolled autoimmune disease Clinically significant cardiac/cardiovascular disease, or pulmonary compromise Seizure disorder History of stroke with the past 6 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 or HBV-DNA is negative and patient is receiving Hep B reactivation prophylaxis. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, and 8 months after the last dose of study drug Positive urine pregnancy test (ie, urine human chorionic gonadotropin) at screening Live viral vaccine within 2 weeks of the first dose of XmAb13676
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Steve Kye, MD, MPH
Phone
858-243-9970
Email
skye@xencor.com
First Name & Middle Initial & Last Name or Official Title & Degree
Phuong Lee
Phone
858-480-3115
Ext
215
Email
plee@xencor.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steve Kye, MD, MPH
Organizational Affiliation
Executive Medical Director, Clinical Development, Xencor, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Moores UC San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Withdrawn
Facility Name
The University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Roswell Park Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Ohio State University Wexner Medical Center and James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
UVA Health System, Division of Hematology & Oncology
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Completed
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Recruiting
Facility Name
Froedtert Hospital and Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Name
Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Name
Hopital Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Paoli Calmette Dpt of Oncology/Hematology
City
Marseille Cedex 9
ZIP/Postal Code
13273
Country
France
Individual Site Status
Recruiting
Facility Name
Chu Montpellier, Hematologie Clinique St. Eloi
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Antoine Lacassagne
City
Nice Cedex
ZIP/Postal Code
06189
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Haut-Leveque, Service d'Hematologie Clinique et Therapie Cellulaire
City
Pessac
ZIP/Postal Code
33604
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Lyon-Sud, Service d'Hematologie
City
Pierre-Benite Cedex
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Individual Site Status
Recruiting
Facility Name
Institut Universitaire du Cancer Toulouse Oncopole
City
Toulouse
ZIP/Postal Code
31100
Country
France
Individual Site Status
Recruiting
Facility Name
CLCC Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Name
Inje University Busan Paik Hospital
City
Busan
ZIP/Postal Code
47392
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Dong A University Medical Center (Dong A University Hospital)
City
Busan
ZIP/Postal Code
49201
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Gachon University Gil Medical Center
City
Incheon
ZIP/Postal Code
21565
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University College of Medicine, Seoul National University Bungdang Hospital
City
Seongnam-si
ZIP/Postal Code
13620
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
The Catholic University of Korea, Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Ewha Womans University Mokdong Hospital
City
Seoul
ZIP/Postal Code
07985
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Royal Marsden Hospital (RMH) - Royal Marsden NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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