Anti-CD30 biAb-AATC in Patients With Relapsed/Refractory CD30 Positive Hematopoietic Malignancies

NCT05544968 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00052928
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

CD30+ Anaplastic Large Cell Lymphoma; CD30+ Pleomorphic Large T-Cell Cutaneous Lymphoma; Hodgkin Disease; CD30-Positive Diffuse Large B-Cell Lymphoma; CD30+ Immunoblastic Large T-Cell Cutaneous Lymphoma; Leukemia; Lymphoma

Keywords

CD30; Cancer; Bispecific; Cellular Therapy; T Cell; autologous; relapse; refractory

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Study Arms (5)

CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)

EXPERIMENTAL

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Drug: GM-CSF

CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)

EXPERIMENTAL

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Drug: GM-CSF

CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)

EXPERIMENTAL

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Drug: GM-CSF

CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)

EXPERIMENTAL

Patients will undergo weekly administration of dose escalating CD30 biAb-AATC infusions with twice weekly subcutaneous GM-CSF (250 μg/m\^2) in 4-week cycles for a maximum of two total cycles. A standard 3+3 dose escalation design will be utilized for this study.

Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Drug: GM-CSF

CD30biAb-AATC Recommended Phase 2 Dose (RP2D)

EXPERIMENTAL

The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed.

Drug: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC); Drug: GM-CSF

Interventions

anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC) DRUG

anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells

Also known as: CD30 biAb-AATC

CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC Recommended Phase 2 Dose (RP2D)

GM-CSF DRUG

Hematopoietic agent that helps form white blood cells.

Also known as: granulocyte-macrophage colony-stimulating factor, sargramostim

CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2); CD30biAb-AATC Recommended Phase 2 Dose (RP2D)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Patients must have had histologic or cytologic verification of the below qualified malignancy. The pathology report for the diagnosis under which the patient is being enrolled and associated molecular diagnostic reports must be submitted.
• a. Hodgkin's Lymphoma (HD): Patients with HD are eligible with one of the following:
• i. Second or greater recurrence or refractory to at least 2 prior therapeutic regimens.
• ii. Any relapse after HSCT.
• b. Non-Hodgkin Lymphoma (NHL): Patients with NHL are eligible with one of the following:
• i. Second or greater recurrence or refractory to at least 2 prior therapeutic regimens.
• ii. Any relapse after HSCT or CAR T cell therapy.
• c. Acute Myeloid Leukemia (AML): Patients with AML are eligible with one of the following:
• i. First or greater relapse.
• ii. Primary refractory disease with at least 1 prior induction attempts.
• d. Acute Lymphoblastic Leukemia (ALL): Patients with ALL are eligible with one of the following:
• i. Second or greater relapse or refractory to at least 2 prior therapeutic regimens.
• ii. Any relapse after HSCT or CAR T cell therapy.
• e. Other Hematopoietic malignancy not listed above for which standard curative measures do not exist, are not proven to prolong survival with an acceptable quality of life, or are no longer effective.
• CD30 Expression Status: Disease specific histologic, cytologic, or Fluorescence-Activated Cell Sorting (FACS)-confirmed CD30 cell surface expression on malignant cells is required. CD30 surface expression must be confirmed at most recent histologic, cytologic, or FACS assessment of disease. This confirmation must occur at recurrence. No repeat CD30 expression verification is required for patients with primary refractory diseases. Pathology and diagnostic reports verifying the CD30 expression status must be submitted.

You may not qualify if:

• Prior Therapy: Any toxicities from prior treatment, \>Grade 3 per CTCAE v5.0 Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T-cell therapy (CAR-T cell) within 60 days of enrollment, or evidence of veno-occlusive disease (VOD) at any time post-transplant.
• Investigational Agent: Treatment with any investigational agent within 14 days of enrollment.
• 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 appropriate anti-fungal antibiotics and adequately controlled. HIV-positive patients on combination antiretroviral therapy are ineligible because of the unknown ability to expand T cell populations for CD30 biAb-AATC product in this setting. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Pulmonary: Prior history of anti-CD30 therapy related pulmonary toxicity.
• Neurologic: Prior history of progressive multifocal leukoencephalopathy (PML).
• Cardiac: Patients diagnosed with NYHA Class III or IV 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Large-Cell, Anaplastic; Leukemia; Lymphoma; Neoplasms; Recurrence

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Hematologic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Guru Subramanian Guru Murthy, MD, MS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Medical College of Wisconsin Cancer Center Clinical Trials Office, MD

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 19, 2022
• Study Start: March 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)