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

Primary Purpose

Acute Myeloid Leukemia, T Cell Acute Lymphoblastic Leukemia, T Cell Lymphoblastic Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
XmAb18968 - Dose level -1
XmAb18968 - Dose level 0 (starting dose)
XmAb18968 - Dose level 1
XmAb18968 - Dose level 2
XmAb18968 - Dose level 3
Sponsored by
Ehab L Atallah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring XmAb18968

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.
  2. Male or female subjects 18 years or older.
  3. 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.
  4. CD38 expression ≥ 20% by flow cytometry or immunohistochemistry at time of relapse.
  5. Adequate organ system function as outlined below:

    1. 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.
    2. Calculated creatinine clearance ≥ 40 mL/min (calculated by Cockcroft-Gault formula) for subjects with creatinine levels above institutional normal.
    3. Ejection > 40% by echocardiogram or multiple-gated acquisition (MUGA) scan.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  7. Female subjects who:

    1. Are postmenopausal for at least one year before the screening visit, OR
    2. Are surgically sterile, OR
    3. 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).

  8. Male subjects, even if surgically sterilized (i.e., status postvasectomy), who:

    1. 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
    2. 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.)

Exclusion Criteria:

  1. Acute promyelocytic leukemia.
  2. 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.
  3. Prior treatment with an anti-CD38 antibody in last 6 months.
  4. 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.
  5. Any serious medical or psychiatric illness that could, in the Investigator's opinion, potentially interfere with the completion of study procedures.
  6. Active, significant, uncontrolled infection. Subjects with infections that are controlled by antibiotics, antiviral or antifungal therapy can be enrolled in the study.
  7. Presence of another active malignancy (requiring treatment) treated within 12 months with the exception of:

    1. Adequately treated non-melanoma skin cancer,
    2. Adequately treated melanoma Grade 2 or less,
    3. Cervical intraepithelial neoplasia,
    4. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast,
    5. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
    6. Adequately treated prostate cancer.
  8. Life-threatening illness with life expectancy < 6 months unrelated to cancer.
  9. Subjects with active central nervous system (CNS) disease. Subjects with adequately treated CNS disease may enroll on the study.
  10. Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection. Note: Subjects who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Subjects who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
  11. Known cardiopulmonary disease defined as:

    1. Unstable angina,
    2. Congestive heart failure (New York Heart Association [NYHA] Class III or IV;
    3. Myocardial infarction (MI) within six months prior to enrollment (subjects 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),
    4. Clinically significant pulmonary hypertension requiring pharmacologic therapy,
    5. Clinically significant arrhythmia:

    i. 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 < Grade 3 A-Fib for a period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen.

  12. Subject 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.
  13. Uncontrolled high blood pressure as determined by the treating physician (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 100 mm Hg).
  14. Subjects with uncontrolled coagulopathy or bleeding disorder.
  15. Known moderate-to-severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
  16. Major surgery within 14 days before the enrollment or a prescheduled major surgery during study period.
  17. Female subjects who are both lactating and breastfeeding or of childbearing potential who have a positive serum or urine test during Screening.
  18. Female subjects who intend to donate eggs (ova) during the course of this study or four months after receiving their last dose of study drug(s).
  19. Male subjects who intend to donate sperm during the course of this study or four months after receiving their last dose of study drug(s).

Sites / Locations

  • Mayo ClinicRecruiting
  • Mayo ClinicRecruiting
  • Moffitt Cancer CenterRecruiting
  • University of Chicago MedicineRecruiting
  • Oregon Health & Science UniversityRecruiting
  • Froedtert Hospital & the Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

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

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

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

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

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

Arm B: Dose Level 1 Group B (AML)

Arm C: Dose Level 2 Group B (AML)

Arm D: Dose Level 3 Group B (AML)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

The number of dose-limiting toxicities for group A level -1
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group A level 0
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group A level 1
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group A level 2
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group A level 3
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group B level -1
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group B level 0
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group B level 1
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group B level 2
See DLT definitions in the detailed study description.
The number of dose-limiting toxicities for group B level 3
See DLT definitions in the detailed study description.
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.
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.

Secondary Outcome Measures

The number of subjects with complete response in group A level -1.
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.
The number of subjects with complete response in group B level -1.
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.
The number of subjects with complete response in group A level 0.
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.
The number of subjects with complete response in group B level 0.
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.
The number of subjects with complete response in group A level 1.
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.
The number of subjects with complete response in group B level 1.
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.
The number of subjects with complete response in group A level 2.
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.
The number of subjects with complete response in group B level 2.
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.
The number of subjects with complete response in group A level 3.
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.
The number of subjects with complete response with incomplete hematological recovery in group A level -1.
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
The number of subjects with complete response with incomplete hematological recovery in group B level -1.
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]).
The number of subjects with complete response with incomplete hematological recovery in group A level 0 (starting dose).
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
The number of subjects with complete response with incomplete hematological recovery in group B level 0 (starting dose).
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
The number of subjects with complete response with incomplete hematological recovery in group A level 1.
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
The number of subjects with complete response with incomplete hematological recovery in group B level 1.
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
The number of subjects with complete response with incomplete hematological recovery in group A level 2.
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
The number of subjects with complete response with incomplete hematological recovery in group B level 2.
All CR criteria except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
The number of subjects with complete response with incomplete hematological recovery in group A level 3.
Meets all criteria for CR except ANC or platelet count.
The number of subjects with complete response with incomplete hematological recovery in group B level 3.
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
Event-free survival (EFS) in group A
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.
Event-free survival (EFS) in group B
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.
Overall survival in group A
The length of time from when a subject begins treatment until death due to any cause.
Overall survival in group B.
The length of time from when a subject begins treatment until death due to any cause.

Full Information

First Posted
September 3, 2021
Last Updated
March 8, 2023
Sponsor
Ehab L Atallah
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1. Study Identification

Unique Protocol Identification Number
NCT05038644
Brief Title
XmAb18968 (CD3-CD38) in Relapsed or Refractory Acute Leukemia and T Cell Lymphoblastic Leukemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 2, 2022 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ehab L Atallah

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, T Cell Acute Lymphoblastic Leukemia, T Cell Lymphoblastic Lymphoma
Keywords
XmAb18968

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm Z: Dose Level -1 for Group A (T-ALL, T-LBL)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm A: Dose Level 0 (Starting Dose) for Group A (T-ALL, T-LBL)
Arm Type
Experimental
Arm Description
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 Title
Arm B: Dose Level 1 for Group A (T-ALL, T-LBL)
Arm Type
Experimental
Arm Description
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 Title
Arm C: Dose Level 2 Group A (T-ALL, T-LBL)
Arm Type
Experimental
Arm Description
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 Title
Arm D: Dose Level 3 Group A (T-ALL, T-LBL)
Arm Type
Experimental
Arm Description
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 Title
Arm Z: Dose Level -1 Group B (AML)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm A: Dose Level 0 (Starting Dose) Group B (AML)
Arm Type
Experimental
Arm Description
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 Title
Arm B: Dose Level 1 Group B (AML)
Arm Type
Experimental
Arm Description
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 Title
Arm C: Dose Level 2 Group B (AML)
Arm Type
Experimental
Arm Description
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 Title
Arm D: Dose Level 3 Group B (AML)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
XmAb18968 - Dose level -1
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
XmAb18968 - Dose level 0 (starting dose)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
XmAb18968 - Dose level 1
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
XmAb18968 - Dose level 2
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
XmAb18968 - Dose level 3
Intervention Description
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.
Primary Outcome Measure Information:
Title
The number of dose-limiting toxicities for group A level -1
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group A level 0
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group A level 1
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group A level 2
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group A level 3
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group B level -1
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group B level 0
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group B level 1
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group B level 2
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
The number of dose-limiting toxicities for group B level 3
Description
See DLT definitions in the detailed study description.
Time Frame
4 Years
Title
Recommended Phase 2 Dose for Group A
Description
This dose will be dependent on the number of dose-limiting toxicities reported in primary outcomes 1-5.
Time Frame
4 Years
Title
Recommended Phase 2 Dose for Group B
Description
This dose will be dependent on the number of dose-limiting toxicities reported in primary outcomes 6-10.
Time Frame
4 Years
Secondary Outcome Measure Information:
Title
The number of subjects with complete response in group A level -1.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group B level -1.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group A level 0.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group B level 0.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group A level 1.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group B level 1.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group A level 2.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group B level 2.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response in group A level 3.
Description
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.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group A level -1.
Description
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group B level -1.
Description
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]).
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group A level 0 (starting dose).
Description
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group B level 0 (starting dose).
Description
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group A level 1.
Description
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group B level 1.
Description
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group A level 2.
Description
Meets all criteria for CR except absolute neutrophil count (ANC) or platelet count.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group B level 2.
Description
All CR criteria except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group A level 3.
Description
Meets all criteria for CR except ANC or platelet count.
Time Frame
4 Years
Title
The number of subjects with complete response with incomplete hematological recovery in group B level 3.
Description
All complete response (CR criteria) except for residual neutropenia (< 1.0 × 109/L [1,000/μL]) or thrombocytopenia (< 100 × 109/L [100,000/μL]).
Time Frame
4 Years
Title
Event-free survival (EFS) in group A
Description
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.
Time Frame
4 Years
Title
Event-free survival (EFS) in group B
Description
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.
Time Frame
4 Years
Title
Overall survival in group A
Description
The length of time from when a subject begins treatment until death due to any cause.
Time Frame
4 Years
Title
Overall survival in group B.
Description
The length of time from when a subject begins treatment until death due to any cause.
Time Frame
4 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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: 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.) 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: 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. Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection. Note: Subjects who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Subjects who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load. Known cardiopulmonary disease defined as: Unstable angina, Congestive heart failure (New York Heart Association [NYHA] Class III or IV; Myocardial infarction (MI) within six months prior to enrollment (subjects 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), Clinically significant pulmonary hypertension requiring pharmacologic therapy, Clinically significant arrhythmia: i. 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 < Grade 3 A-Fib for a period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen. Subject 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). Subjects with uncontrolled coagulopathy or bleeding disorder. Known moderate-to-severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis. Major surgery within 14 days before the enrollment or a prescheduled major surgery during study period. Female subjects who are both lactating and breastfeeding or of childbearing potential who have a positive serum or urine test during Screening. Female subjects who intend to donate eggs (ova) during the course of this study or four months after receiving their last dose of study drug(s). Male subjects who intend to donate sperm during the course of this study or four months after receiving their last dose of study drug(s).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical College of Wisconsin Cancer Center Clinical Trials Office
Phone
866-680-0505
Ext
8900
Email
cccto@mcw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ehab Atallah, MD
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cecilia Arana-Yi, MD
Phone
505-272-4946
Email
aranayi.cecilia@mayo.edu
First Name & Middle Initial & Last Name & Degree
Robert (Robby) Bennett III
Phone
480-342-6641
Email
BennettIII.Robert@mayo.edu
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Talha Badar, MD
Phone
713-745-4428
Email
badar.talha@mayo.edu
First Name & Middle Initial & Last Name & Degree
Taylor Stair
Phone
904-953-3007
Email
stair.taylor@mayo.edu
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bijal Shah, MD
Phone
813-745-4294
Email
Bijal.Shah@moffitt.org
First Name & Middle Initial & Last Name & Degree
Hannah Lewis
Email
Hannah.Lewis@moffitt.org
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam DuVall, MD
Email
duvalla@bsd.uchicago.edu
First Name & Middle Initial & Last Name & Degree
Howie Weiner
Phone
708-220-0359
Email
hweiner@bsd.uchicago.edu
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Leonard, MD
Phone
503-494-4016
Email
leonard@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Alyssia Carlson
Phone
503-494-2166
Email
carlsaly@ohsu.edu
Facility Name
Froedtert Hospital & the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Althea Thomas, RN
Phone
414-805-2588
Email
athomas@mcw.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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