CD30biAb-AATC for CD30+ Malignancies

Phase I Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of Anti-CD30 Bispecific Antibody-armed Anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC) in Patients With Relapsed/Refractory CD30 Positive Hematopoietic Malignancies

This first-in-human trial will assess the safety, feasibility, and efficacy of an immunotherapy with a novel CD30 antibody conjugated to a CD3 antibody that is preloaded onto a patient's own T-cells, generating a CD30 bispecific antibody-armed, anti-CD3-activated, autologous T-cells (CD30 biAb-AATC).

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; Leukemia; Hodgkin Disease; CD30-Positive Diffuse Large B-Cell Lymphoma; CD30+ Anaplastic Large Cell Lymphoma; CD30+ Pleomorphic Large T-Cell Cutaneous Lymphoma; CD30+ Immunoblastic Large T-Cell Cutaneous Lymphoma
• Intervention / Treatment: Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)

Detailed Description

Non-randomized, single arm, dose escalating, Phase I study evaluating the feasibility and safety of a novel anti-CD30 biAb-AATC product for adult patients with relapsed/refractory CD30+ cancer. Following T-cell collection patients are recommended to receive a bridging chemotherapy for 21 days while product is being generated and quality control assessed. Patients will then undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF in 4-week cycles for a maximum of two total cycles.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Coordinator; Phone Number: 414-266-4170; Email: MACCCTO@MCW.edu
• Study Contact Backup: Name: Nathan Schloemer, MD; Phone Number: 414-266-4170; Email: nschloem@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Wisconsin
      • Contact: Nathan Schloemer; Phone Number: 414-266-2420

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 39 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis: Patients must have had histologic or cytologic verification of a qualified malignancy at original diagnosis. Patients must have histologic or cytologic verification of recurrence at relapse. No additional biopsy is required for patients with primary refractory diseases. The pathology report for the diagnosis under which the patient is being enrolled and associated molecular diagnostic reports must be submitted.
• CD30 Expression Status : Disease specific histologic, cytologic, or Fluorescence-Activated Cell Sorting (FACS)-confirmed CD30 cell surface expression on malignant cells is required.

• Disease Status:

  i. Lymphomas: Patients must have measurable disease for assessment of radiographic response defined as either nodal disease >/=1.5 cm or extranodal lesion >/=1.0 cm.

ii. Leukemias: Patients must have relapsed/refractory (including MRD >0.01% by flow cytometry) disease.

• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anticancer chemotherapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria prior to entering this study
• Age: Patients must be ≥ 18 years at time of study enrollment.
• Life Expectancy: Life expectance of >12 weeks.
• Performance Status: Karnofsky ≥50% for patients. Note: Neurologic deficits in patients with CNS involvement must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Organ Function Requirements: Have acceptable organ function
• Pregnancy: It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment.
• Consent: Ability to under understand a written informed consent document, and the willingness to sign it. Voluntary written consent will be documented before initiation of study-related procedures not part of normal medical care. Consent may be withdrawn by the subject/guardian without prejudice to future medical care.

Exclusion Criteria:

• Prior Therapy: Any toxicities from prior treatment, >Grade 3 per CTCAE v5.0
• Investigational Agent: Treatment with any investigational agent within 14 days of enrollment.
• Exclusion Requirements Due to Comorbid Disease or Concurrent Illness:

Immune: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Steroid premedication for imaging scans is allowed. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Infectious: 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). Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.

Pulmonary: No current or prior history of anti-CD30 therapy related pulmonary toxicity.

Neurologic: No current or prior history of progressive multifocal leukoencephalopathy (PML).

Cardiac: Patients cannot be diagnosed with NYHA Class III or IV (Appendix 5) congestive heart failure, ventricular arrhythmias, or uncontrolled hypertension.

• Allergies: Known hypersensitivity or allergic reaction attributed to any of the components of CD30 biAb-AATC or to compounds of similar composition to CD30 targeted agent, or a bispecific Antibody-armed activated autologous T cell product.
• Pregnant or Breastfeeding: Pregnant or breastfeeding females will not be allowed to enroll on this study. Female patients with infants must agree not to breastfeed their infants during the entire study treatment period and through three months after the last study drug dose. Agents used in this study are known to be teratogenic to a fetus. There is there is no information on the excretion of CD30 biAb-AATC agents into breast milk but potential risk for adverse events in nursing infants secondary to treatment of the mother with a CD30 biAb-AATC.
• Secondary Malignancy: Patients should not have a history of any second malignancy in the last 1 year with exception of the diagnosis for inclusion; subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD30biAb-AATC; Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF in 4-week cycles for a maximum of two total cycles.	Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Other Names: CD30 biAb-AATC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	To determine the MTD and recommended Phase II dose of CD30 biAb-AATC administered once weekly for a total of 4 doses per cycle	3 years
Define Toxicities - CTCAE v5.0	To define the toxicities of CD30 biAb-AATC with twice weekly subcutaneous GM-CSF	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of CD30 biAb-AATC - Cmax	To define the circulating pharmacokinetics of CD30 biAb-AATC with twice weekly subcutaneous GM-CSF. Determination of peak plasma concentration	3 years
Pharmacokinetics of CD30 biAb-AATC - AUC(0-28day)	To define the circulating pharmacokinetics of CD30 biAb-AATC with twice weekly subcutaneous GM-CSF. Determination of persistence through AUC (0-28 day)	3 years
Define anti-tumor activity - Time-to-event efficacy	Within the confines of this Phase I study, to define the antitumor activity of anti-CD30 biAb-AATC in patients with CD30+ recurrent and/or refractory malignancies	3 years
Define anti-tumor activity - Objective Response Rate	Within the confines of this Phase I study, to define the antitumor activity of anti-CD30 biAb-AATC in patients with CD30+ recurrent and/or refractory malignancies	3 years
In vitro activity - quantitative cytotoxicity	To define the in vitro antitumor activity of a primary patient CD30 biAb-AATC product against standardized CD30+ cellular targets	3 years

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Collaborators: Midwest Athletes Against Childhood Cancer
• Investigators: Principal Investigator: Nathan Schloemer, MD, Medical College of Wisconsin / Children's Wisconsin

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; relapse; T Cell; refractory; autologous; Cellular Therapy; Bispecific; CD30
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Hodgkin Disease; Lymphoma, T-Cell, Cutaneous; Lymphoma, Large-Cell, Anaplastic; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Bispecific
• Other Study ID Numbers: IIT-SCHLOEMER-BAAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No