A Phase I 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
Overview
- Phase
- Phase 1
- Intervention
- anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
- Conditions
- Hodgkin Disease
- Sponsor
- Medical College of Wisconsin
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Not yet recruiting
- Last Updated
- 3 months ago
Overview
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).
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.
Investigators
Guru Subramanian Guru Murthy
Associate Professor
Medical College of Wisconsin
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
- •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 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.
Arms & Interventions
CD30biAb-AATC Recommended Phase 2 Dose (RP2D)
The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed.
Intervention: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
CD30biAb-AATC Recommended Phase 2 Dose (RP2D)
The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed.
Intervention: GM-CSF
CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
CD30biAb-AATC (Dose Level -1 -- 40 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: GM-CSF
CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
CD30biAb-AATC (Dose Level 1 -- 80 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: GM-CSF
CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
CD30biAb-AATC (Dose Level 2 -- 120 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: GM-CSF
CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
CD30biAb-AATC (Dose Level 3 -- 160 x 10^6 cells/kg/infusion + GM-CSF 250 μg/m^2)
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.
Intervention: GM-CSF
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: 2 years
To determine the MTD and recommended Phase II dose of CD30 biAb-AATC administered once weekly for a total of 4 doses per cycle