XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia

NCT05038644 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO00041908
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 6

Brief 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).

Conditions

Acute Myeloid Leukemia; T Cell Acute Lymphoblastic Leukemia; T Cell Lymphoblastic Lymphoma

Keywords

XmAb18968

Outcome Measures

Primary Outcomes (12)

• The number of dose-limiting toxicities for group A level -1

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group A level 0

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group A level 1

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group A level 2

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group A level 3

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group B level -1

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group B level 0

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group B level 1

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group B level 2

  See DLT definitions in the detailed study description.

  4 Years

• The number of dose-limiting toxicities for group B level 3

  See DLT definitions in the detailed study description.

  4 Years

• Recommended Phase 2 Dose for Group A

  This dose will be dependent on the number of dose-limiting toxicities reported in primary outcomes 1-5.

  4 Years

• Recommended Phase 2 Dose for Group B

  This dose will be dependent on the number of dose-limiting toxicities reported in primary outcomes 6-10.

  4 Years

Secondary Outcomes (23)

• The number of subjects with complete response in group A level -1.

  4 Years

• The number of subjects with complete response in group B level -1.

  4 Years

• The number of subjects with complete response in group A level 0.

  4 Years

• The number of subjects with complete response in group B level 0.

  4 Years

• The number of subjects with complete response in group A level 1.

  4 Years

Study Arms (10)

Arm Z: Dose Level -1 for Group A (T-ALL, T-LBL)

EXPERIMENTAL

0.1 mg intravenous (IV) Cycle (C) 1 Day (D) 1, 0.3 mg IV C1D2, then 0.4 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level -1

Arm A: Dose Level 0 (Starting Dose) for Group A (T-ALL, T-LBL)

EXPERIMENTAL

0.2 mg IV C1D1, 0.6 mg IV C1D2, then 0.8 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 0 (starting dose)

Arm B: Dose Level 1 for Group A (T-ALL, T-LBL)

EXPERIMENTAL

0.25 mg IV C1D1, 0.75 mg IV C1D2, then 1.0 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 1

Arm C: Dose Level 2 Group A (T-ALL, T-LBL)

EXPERIMENTAL

0.4 mg IV C1D1, 0.9 mg IV C1D2, then 1.3 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 2

Arm D: Dose Level 3 Group A (T-ALL, T-LBL)

EXPERIMENTAL

0.5 mg IV C1D1, 1.0 mg IV C1D2, then 1.5 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 3

Arm Z: Dose Level -1 Group B (AML)

EXPERIMENTAL

0.1 mg IV C1D1, 0.3 mg IV C1D2, then 0.4 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level -1

Arm A: Dose Level 0 (Starting Dose) Group B (AML)

EXPERIMENTAL

0.2 mg IV C1D1, 0.6 mg IV C1D2, then 0.8 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 0 (starting dose)

Arm B: Dose Level 1 Group B (AML)

EXPERIMENTAL

0.25 mg IV C1D1, 0.75 mg IV C1D2, then 1.0 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 1

Arm C: Dose Level 2 Group B (AML)

EXPERIMENTAL

0.4 mg IV C1D1, 0.9 mg IV C1D2, then 1.3 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 2

Arm D: Dose Level 3 Group B (AML)

EXPERIMENTAL

0.5 mg IV C1D1, 1.0 mg IV C1D2, then 1.5 mg IV on D8, D15, and D22 in a 28-day cycle.

Drug: XmAb18968 - Dose level 3

Interventions

XmAb18968 - Dose level 1 DRUG

0.25 mg IV C1D1, 0.75 mg IV C1D2, then 1.0 mg IV on D8, D15, and D22 in a 28-day cycle.

Arm B: Dose Level 1 Group B (AML); Arm B: Dose Level 1 for Group A (T-ALL, T-LBL)

XmAb18968 - Dose level 0 (starting dose) DRUG

0.2 mg IV C1D1, 0.6 mg IV C1D2, then 0.8 mg IV on D8, D15, and D22 in a 28-day cycle.

Arm A: Dose Level 0 (Starting Dose) Group B (AML); Arm A: Dose Level 0 (Starting Dose) for Group A (T-ALL, T-LBL)

XmAb18968 - Dose level 2 DRUG

0.4 mg IV C1D1, 0.9 mg IV C1D2, then 1.3 mg IV on D8, D15, and D22 in a 28-day cycle.

Arm C: Dose Level 2 Group A (T-ALL, T-LBL); Arm C: Dose Level 2 Group B (AML)

XmAb18968 - Dose level 3 DRUG

0.5 mg IV C1D1, 1.0 mg IV C1D2, then 1.5 mg IV on D8, D15, and D22 in a 28-day cycle.

Arm D: Dose Level 3 Group A (T-ALL, T-LBL); Arm D: Dose Level 3 Group B (AML)

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.
• Male or female subjects 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 below:
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN. If total bilirubin \> 1.5 × ULN then check direct bilirubin. Subject will be eligible if direct bilirubin is \< 1.5 × ULN.
• Calculated creatinine clearance ≥ 40 mL/min (calculated by Cockcroft-Gault formula) for subjects with creatinine levels above institutional normal.
• Ejection \> 40% by echocardiogram or multiple-gated acquisition (MUGA) scan.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential:
• i. 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 subjects, even if surgically sterilized (i.e., status postvasectomy), who:

You may not qualify if:

• 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:
• Adequately treated non-melanoma skin cancer,
• Adequately treated melanoma Grade 2 or less,
• Cervical intraepithelial neoplasia,
• Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast,
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
• Adequately treated prostate cancer.
• Life-threatening illness with life expectancy \< 6 months unrelated to cancer.
• Subjects with active central nervous system (CNS) disease. Subjects with adequately treated CNS disease may enroll on the study.

Sponsors & Collaborators

• Ehab L Atallah: lead

Study Sites (6)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ehab Atallah, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 9, 2021
• Study Start: February 2, 2022
• Primary Completion: April 24, 2024
• Study Completion: November 18, 2024
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)