Back to resultsStudy of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
Primary Purpose
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ADCT-301
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Camidanlumab tesirine
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory CD25-positive AML [per World Health Organization (WHO)].
- Relapsed or refractory CD25-positive ALL [per World Health Organization (WHO)].
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Creatinine ≤1.5mg/dL.
- Serum/plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement.
- Total serum/plasma bilirubin ≤1.5 times the upper limit of normal.
- Women of childbearing potential must have a negative urine or serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
- Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.
- White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.
Exclusion Criteria:
- Participants who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease.
- Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.
- Active graft versus host disease.
- Autologous or allogenic transplant within the 60 days prior to Screening.
- Known history of immunogenicity or hypersensitivity to a CD25 antibody.
- Known history of positive serum human anti-drug antibodies (ADA), or known allergy to any component of ADCT-301.
- Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy.
- History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
- Pregnant or breastfeeding women.
- Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
- Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case < 14 days prior to the start of the study treatment on Cycle 1, Day 1.
- Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted therapies within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.
- Failure to recover (to CTCAE Version 4.0 Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
- Isolated extramedullary relapse (i.e., testicular, CNS).
- Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening (unless secondary to pacemaker or bundle branch block).
- Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy.
- Any other significant medical illness, abnormality, or condition.
Sites / Locations
- Winship Cancer Institute, Emory University
- Northside Hospital
- The University of Chicago Medical Center
- Memorial Sloan Kettering Cancer Center
- Duke Cancer Center
- Greenville Health System, Institute for Translational Oncology Research
- The University of Texas M.D. Anderson Cancer Center
- Virginia Cancer Specialists, PC
- Swedish Cancer Institute
- University of Washington Medical Center
- Froedtert Hospital/ Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1: ADCT-301 (dose escalation)
Part 2: ADCT-301 (dose expansion)
Arm Description
Weekly administration - Participants will receive an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle. 3-week administration - Participants will receive an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle. The dose escalation will be conducted according to a 3+3 design.
Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee.
Outcomes
Primary Outcome Measures
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes:
A hematologic DLT is defined as:
- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with <5% blasts). In case of a normocellular bone marrow with <5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT.
A non-hematologic DLT is defined as:
Grade 4 tumor lysis syndrome.
Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia).
CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication).
CTCAE Grade 3 or higher skin ulceration.
Peripheral sensory or motor neuropathy ≥ Grade 2.
Recommended Dose of ADCT-301 for Part 2
The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)
An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.
Secondary Outcome Measures
Duration of Response (DOR)
DOR is defined among responders (complete response [CR], CR with incomplete blood count recover [CRi], or partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
CR:
Bone marrow differential showing ≤5% blast cells.
Absolute neutrophil count (ANC) ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L.
Absence of extramedullary disease.
Participant is independent of red blood cell transfusions.
CRi is defined as achieving all CR criteria except that values for ANC may be <1.0 x 10^9/L and/or values for platelets may be <100 x 10^9/L.
PR:
ANC ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L.
Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level >5% and ≤25%, or bone marrow differential showing <5% blast cells.
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders.
Overall Survival (OS)
OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Number of Participants With Progression Free Survival (PFS)
PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts.
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1.
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Clearance (CL) for ADCT-301 for the QW Dosing Schedule
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Number of Participants With Anti-drug Antibody Response (Against ADCT-301)
Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol.
Full Information
NCT ID
NCT02588092
First Posted
August 13, 2015
Last Updated
February 12, 2020
Sponsor
ADC Therapeutics S.A.
1. Study Identification
Unique Protocol Identification Number
NCT02588092
Brief Title
Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
Official Title
A Phase 1, Open-label, Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Activity of ADCT 301 in Patients With Relapsed or Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow enrollment
Study Start Date
February 1, 2016 (Actual)
Primary Completion Date
August 29, 2018 (Actual)
Study Completion Date
August 29, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ADC Therapeutics S.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). Participants will participate in a dose-escalation phase (Part 1) and receive ADCT-301 either weekly or once every 3 weeks.
In Part 2 of the study, participants will receive a recommended dose of ADCT-301 as determined by a Dose Escalation Steering Committee.
Detailed Description
This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and pharmacokinetics of ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL).
ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication.
The study will be conducted in 2 parts: In Part 1 (dose escalation) participants will either be on weekly administration or every 3-week administration. Participants on weekly administration will receive an infusion of ADCT-301 on Days 1, 8, and 15 of each 3 week treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-301 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.
In Part 2 (expansion), participants will be assigned to receive a recommended dose and/or schedule of ADCT-301 as determined by a Dose Escalation Steering Committee.
For each participant, the study will include a screening period (up to 28 days), a treatment period, and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall participant tolerability to the study drug and response to treatment. It is anticipated that the entire study (Parts 1 and 2) will enroll a maximum of 80 participants and could last approximately 3 years from first participant treated to last participant completed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
Keywords
Camidanlumab tesirine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: ADCT-301 (dose escalation)
Arm Type
Experimental
Arm Description
Weekly administration - Participants will receive an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle.
3-week administration - Participants will receive an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle.
The dose escalation will be conducted according to a 3+3 design.
Arm Title
Part 2: ADCT-301 (dose expansion)
Arm Type
Experimental
Arm Description
Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee.
Intervention Type
Drug
Intervention Name(s)
ADCT-301
Other Intervention Name(s)
Camidanlumab tesirine
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
Description
A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes:
A hematologic DLT is defined as:
- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with <5% blasts). In case of a normocellular bone marrow with <5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT.
A non-hematologic DLT is defined as:
Grade 4 tumor lysis syndrome.
Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia).
CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication).
CTCAE Grade 3 or higher skin ulceration.
Peripheral sensory or motor neuropathy ≥ Grade 2.
Time Frame
Day 1 to Day 21 (Cycle 1)
Title
Recommended Dose of ADCT-301 for Part 2
Description
The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.
Time Frame
Day 1 to Day 21 (Cycle 1)
Title
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
Description
A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Time Frame
Day 1 to a maximum of 24 weeks (+ 30 days)
Title
Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)
Description
An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.
Time Frame
Day 1 to a maximum of 24 weeks (+ 30 days)
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
DOR is defined among responders (complete response [CR], CR with incomplete blood count recover [CRi], or partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
CR:
Bone marrow differential showing ≤5% blast cells.
Absolute neutrophil count (ANC) ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L.
Absence of extramedullary disease.
Participant is independent of red blood cell transfusions.
CRi is defined as achieving all CR criteria except that values for ANC may be <1.0 x 10^9/L and/or values for platelets may be <100 x 10^9/L.
PR:
ANC ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L.
Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level >5% and ≤25%, or bone marrow differential showing <5% blast cells.
Time Frame
Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders.
Time Frame
Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Title
Overall Survival (OS)
Description
OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Time Frame
Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Title
Number of Participants With Progression Free Survival (PFS)
Description
PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Time Frame
Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Title
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
Description
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
Description
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
Description
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
Description
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule
Description
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule
Description
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule
Description
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule
Description
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
Description
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
Description
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
Description
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
Description
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
Description
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
Description
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
Description
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
Description
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
Description
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
Description
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
Description
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
Description
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
Description
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time Frame
Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Clearance (CL) for ADCT-301 for the QW Dosing Schedule
Description
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time Frame
Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Title
Number of Participants With Anti-drug Antibody Response (Against ADCT-301)
Description
Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol.
Time Frame
Day 1 to the end of Cycle 2 (6 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory CD25-positive AML [per World Health Organization (WHO)].
Relapsed or refractory CD25-positive ALL [per World Health Organization (WHO)].
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Creatinine ≤1.5mg/dL.
Serum/plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement.
Total serum/plasma bilirubin ≤1.5 times the upper limit of normal.
Women of childbearing potential must have a negative urine or serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.
Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.
White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.
Exclusion Criteria:
Participants who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease.
Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.
Active graft versus host disease.
Autologous or allogenic transplant within the 60 days prior to Screening.
Known history of immunogenicity or hypersensitivity to a CD25 antibody.
Known history of positive serum human anti-drug antibodies (ADA), or known allergy to any component of ADCT-301.
Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy.
History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.
Pregnant or breastfeeding women.
Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.
Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case < 14 days prior to the start of the study treatment on Cycle 1, Day 1.
Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted therapies within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.
Failure to recover (to CTCAE Version 4.0 Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
Isolated extramedullary relapse (i.e., testicular, CNS).
Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening (unless secondary to pacemaker or bundle branch block).
Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy.
Any other significant medical illness, abnormality, or condition.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron Goldberg, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60647
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
Country
United States
Facility Name
Duke Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Greenville Health System, Institute for Translational Oncology Research
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
The University of Texas M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Cancer Specialists, PC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Froedtert Hospital/ Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32521310
Citation
Goldberg AD, Atallah E, Rizzieri D, Walter RB, Chung KY, Spira A, Stock W, Tallman MS, Cruz HG, Boni J, Havenith KEG, Chao G, Feingold JM, Wuerthner J, Solh M. Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study. Leuk Res. 2020 Aug;95:106385. doi: 10.1016/j.leukres.2020.106385. Epub 2020 Jun 7.
Results Reference
derived
Learn more about this trial
Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
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