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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.

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.

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.

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.

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.

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.

XmAb18968 - Dose level -1

XmAb18968 - Dose level 0 (starting dose)

XmAb18968 - Dose level 1

XmAb18968 - Dose level 2

XmAb18968 - Dose level 3

Medical College of Wisconsin Cancer Center Clinical Trials Office

Cecilia Arana-Yi, MD

Robert (Robby) Bennett III

Talha Badar, MD

Taylor Stair

Bijal Shah, MD

Hannah Lewis

Adam DuVall, MD

Howie Weiner

Jessica Leonard, MD

Alyssia Carlson

Althea Thomas, RN

Ehab Atallah, MD

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).

The primary objective of this portion of the study is to determine a recommended phase II dose (RP2D) for XmAb18968. The trial will use a variation of the 3 + 3 design where both escalation and de-escalation are possible. There will be separate cohorts; Group A (T cell acute lymphoblastic leukemia, T cell lymphoblastic lymphoma) and Group B (acute myeloid leukemia). A minimum of 24 and a maximum of 60 subjects will be needed for the study.

The first dose on Cycle 1 Day 1 (C1D1) will be split into two doses to ensure the safety of subjects and to closely monitor for CRS. The dose will be split into C1D1 and Cycle 1 Day 2 (C1D2) with approximately 25% of the dose given on C1D1 and 75% of the dose given on C1D2. Thereafter, subjects will receive the full dose planned for that cohort.

Prior to enrolling subjects at the next applicable dose level, the Data Safety Monitoring Committee (DSMC) will review the results.

Although AEs may occur at any point during treatment, only AEs occurring during Cycle 1 of treatment will necessarily influence decisions regarding dose escalation, expansion of a dose level, or evaluation of intermediate dose levels. Subjects will be monitored through all cycles of therapy for treatment-related toxicities.

Toxicity will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. If multiple AEs are seen, the presence of a DLT will be based on the most severe AE experienced. The DLT will be based on the tolerability observed during the first 28 days (or up to 42 days for hematological DLTs) of treatment/observation.

DLT will be defined as any of the following events:

* Any grade 4 or higher non-hematological adverse reaction.
* Cytokine release syndrome (CRS) is a possible side effect that can occur as a result of administration of XmAb18968. For this protocol, any grade 3 or higher CRS adverse event (AE) (per revised CRS grading system will be considered a DLT except grade 3 CRS AE that resolves to grade 1 within seven days).
* Any subject meeting the criteria for Hy's Law case (i.e., severe drug-induced liver injury (DILI)). A Hy's Law case is defined as: aspartate aminotransferase (AST) or alanine transaminase (ALT) values ≥ 3 × upper limit of normal (ULN) AND with serum total bilirubin (TBIL) level \> 2 × ULN or international normalized ratio (INR) \> 1.5 without signs of cholestasis.
* Any non-Hy's Law grade 3 liver abnormality lasting more than 72 hours will be considered a DLT.
* Grade 3 electrolyte abnormalities - sodium (Na), potassium (K), chloride (Cl), carbon dioxide (CO2), calcium (Ca), magnesium (Mg), phosphate - that do not return to grade 1 or lower within 72 hours.
* Any grade 4 neurotoxicity will be considered a DLT. Grade 3 neurotoxicity that lasts more than 72 hours will be considered a DLT.
* Any grade 3 nausea, vomiting, or diarrhea that requires hospitalization, tube feeding or total parenteral nutrition.
* Any adverse reaction that leads to dose reduction or withdrawal.
* Grade 3 transaminitis (AST/ALT) elevation that does not return to grade 1 or lower within 72 hours.
* Any grade 3 infection lasting more than seven days in the absence of active leukemia.
* Any grade 3 bleeding with thrombocytopenia in the absence of active leukemia.
* Any grade 4 or higher neutropenia lasting past cycle day 42 in the absence of active leukemia.

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

MCW-XEN21: 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

See DLT definitions in the detailed study description.

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

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

This is defined as no circulating lymphoblasts or extramedullary disease (no lymphadenopathy, splenomegaly). Testicular mass, skin/gum infiltration, CNS involvement; trilineage hematopoiesis with \< 5% blasts; ANC \> 1.0 × 10\^9/L (1,000/μL); Platelet count \> 100 × 10\^9/L (100,000/μL); No recurrence for four weeks.

This is defined as bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; ANC \> 1.0 × 10\^9/L (1,000/μL); platelet count \> 100 × 10\^9/L (100,000/μL); independence of red cell transfusions.

Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.

All complete response (CR criteria) except for residual neutropenia (\< 1.0 × 10\^9/L \[1,000/μL\]) or thrombocytopenia (\< 100 × 10\^9/L \[100,000/μL\]).

All complete response (CR criteria) except for residual neutropenia (\< 1.0 × 109/L \[1,000/μL\]) or thrombocytopenia (\< 100 × 109/L \[100,000/μL\]).

All CR criteria except for residual neutropenia (\< 1.0 × 109/L \[1,000/μL\]) or thrombocytopenia (\< 100 × 109/L \[100,000/μL\]).

Meets all criteria for CR except ANC or platelet count.

EFS will be defined from the time of achievement of CR/CRi to the time of next relapse/progression/death as measured by the National Comprehensive Cancer Network (NCCN) Response Criteria for Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

EFS will be will be defined from the time of achievement of CR/CRi to the time of next relapse/progression/death as measured by the Response Evaluation Criteria: Acute Myeloid Leukemia.

The length of time from when a subject begins treatment until death due to any cause.

Ehab L Atallah

Professor

Subjects will receive BT-007 CD7 CAR-T cells infusion on Day 0 : 100% of total dose.

T cells purified from the peripheral blood mononuclear cell (PBMC) of subjects or subjects' relatives which depend on their conditions, transduced with 4-1BB/CD3ζ lentiviral vector, expanded in vitro for future administration.

BT-007 CD7 CAR-T cells

Zhongwei Xu, MD, PhD

Weiping Liu, MD, PhD

This is a single center, single arm, open-lable phase I study to determine the safety and efficacy of T cells expressing CD7 chimeric antigen receptors (referred to as "BT-007 CAR-T cells") in patients with relapsed or refractory acute T cell lymphoblastic lymphoma (R/R T-LBL).

Primary objective:

To investigate the safety and efficacy of CD7 CAR-T cells in the treatment of patients with relapsed or refractory acute T cell lymphoblastic lymphoma (R/R T-LBL).

Secondary objective:

To assess the patient's quality of life after receiving the treatment.

Chimeric Antigen Receptor T-Cell (CAR-T) Cells in Patients With R/R T-LBL

Safety and Efficacy of BT-007 CAR-T Cells in the Treatment of Patients With Relapsed/Refractory T Cell Lymphoblastic Lymphoma (R/R T-LBL)

The percentage of participants who achieved complete remission (CR) over all participants.

The tumor status of patient is assessed for the baseline when assigned into treatment group. The overall CR is assessed by the Lugano Classification Lymphoma Response Criteria 2014 on Day 28, Month 3, Month 6, as well as Month 24 for termination. The overall CR is also assessed for the case withdraw from treatment before the termination of 24 months.

The percentage of participants who achieved partial remission (PR) over all participants.

The assessment criteria and time frame are the same as CR.

The retention amount of CAR-T cells in all subjects within 24 months when terminated.

The retention amount of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion. The retention amount is also assessed every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated.

The retention time of CAR-T cells in all subjects within 24 months when terminated.

The retention time of CAR-T cells in all subjects is assessed on Day 1, 7, 14, 28 during first month after cell infusion. The retention time is also assessed every month during Month 2 and 6, and every three months during Month 6 and 24 when terminated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia	NCT05038644	Acute Myeloid L... T Cell Acute Ly... T Cell Lymphobl...	XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos...	18 Years -	Medical College of Wisconsin
XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia	NCT05038644	Acute Myeloid L... T Cell Acute Ly... T Cell Lymphobl...	XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos... XmAb18968 - Dos...	18 Years -	Medical College of Wisconsin
Chimeric Antigen Receptor T-Cell (CAR-T) Cells in Patients With R/R T-LBL	NCT05554575	T Cell Lymphobl...	BT-007 CD7 CAR-...	18 Years - 70 Years	Bioceltech Therapeutics, Ltd.

Spots Global Cancer Trial Database for t cell lymphoblastic lymphoma