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Clinical Trial 21521

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT05038644

Phase: Phase I
Principal Investigator: Shah, Bijal

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Phase 1 Study of XmAb18968 (CD3-CD38) for the Treatment of Patients with Relapsed/Refractory CD38 positive Acute Leukemia and T Cell Lymphoblastic Lymphoma

Summary

This is a phase 1, dose-escalation study (using 3 + 3 dose-limiting toxicity (DLT) criteria) evaluating the safety and tolerability of XmAb18968, as well as establishing a recommended phase II dose (RP2D) in subjects with T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphoblastic (lymphoma) T-LBL (Group A) and acute myeloid leukemia (AML) (Group B).

Objective

Primary Objective: To determine the recommended Phase 2 dose (RP2D) and tolerability profile of XmAb18968 in subjects with relapsed/refractory acute leukemia and T-LBL with CD38 expression Secondary Objectives: Assess the efficacy of XmAb18968 in subjects with relapsed/refractory CD38+ve acute leukemia and T-LBL. Characterize the pharmacokinetics (PK) of XmAb18968.

Treatments

Therapies

Immunotherapy; Therapy (NOS)

Medications

Allopurinol (); Dexamethasone (); Tocilizumab (); XmAb18968 ()

Inclusion Criteria

Inclusion Criteria:

Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.

Male or female patients 18 years or older.

Morphologically documented T-ALL, AML (including undifferentiated leukemia and bi-phenotypic leukemia, or T-LBL in relapsed/refractory status (at least one line of prior therapy). Subjects with measurable residual disease by flow cytometry, molecular testing or cytogenetics will be eligible for the trial.

CD38 expression ≥ 20% by flow cytometry or immunohistochemistry at time of relapse.

Adequate organ system function as outlined in protocol.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Female patients who: (a) Are postmenopausal for at least one year before the screening visit, OR (2) Are surgically sterile, OR If they are of childbearing potential: Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through four months after the last dose of study drug (female and male condoms should not be used together), OR ii. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception).

Male patients, even if surgically sterilized (i.e., status postvasectomy), who agree to practice effective barrier contraception during the entire study drug treatment period from the time of signing the informed consent through four months after the last dose of study drug (female and male condoms should not be used together), OR Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)

Other criteria may apply

Exclusion Criteria

Exclusion Criteria:

Acute promyelocytic leukemia.

Treatment with systemic antineoplastic therapy within 5 half-lives from the last dose before cycle one day one of therapy. Radiation within 7 days before C1D1 of therapy. The use of hydroxyurea, steroids, or vincristine for leukoreduction is permitted.

Prior treatment with an anti-CD38 antibody in last 6 months.

Hematopoietic stem cell transplantation within 6 months of enrollment, or evidence of veno-occlusive disease at any time post-transplant, or active graft-versus-host disease requiring immunosuppressive therapy.

Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of study procedures.

Active, significant, uncontrolled infection. Subjects with infections that are controlled by antibiotics, antiviral or antifungal therapy can be enrolled in the study.

Presence of another active malignancy (requiring treatment) treated within 12 months with the exception of: (a) Adequately treated non-melanoma skin cancer, (b) Adequately treated melanoma Grade 2 or less, (c) Cervical intraepithelial neoplasia, (d) Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast, (e) Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, (f) Adequately treated prostate cancer.

Life-threatening illness with life expectancy > Patients with active central nervous system (CNS) disease. Subjects with adequately treated CNS disease may enroll on the study.

Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection.

Known cardiopulmonary disease defined as: (a) Unstable angina, (b) Congestive heart failure (New York Heart Association [NYHA] Class III or IV; (c) Myocardial infarction (MI) within six months prior to enrollment (patients who had ischemic heart disease such as acute coronary syndrome, MI, and/or revascularization > 6 months before Screening and who are without cardiac symptoms may enroll), (d) Clinically significant pulmonary hypertension requiring pharmacologic therapy, (e) Clinically significant arrhythmia:

History of polymorphic ventricular fibrillation or torsade de pointes, ii. Uncontrolled permanent atrial fibrillation (A-Fib), defined as continuous A-Fib for ≥ 6 months and not well controlled with adequate A-Fib therapy, iii. Uncontrolled persistent A-Fib, defined as sustained A-Fib lasting > 7 days and/or requiring cardioversion in the four weeks before Screening and not well controlled with A-Fib therapy, iv. Grade 3 A-Fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker), or ablation, and v. Subjects with paroxysmal A-Fib or > Patient has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, gastrointestinal or any other medical condition that in the opinion of the Investigator would adversely affect his/her participating in this study.

Uncontrolled high blood pressure as determined by the treating physician (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 100 mm Hg).

Patients with uncontrolled coagulopathy or bleeding disorder.

Other criteria apply

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