Acute Myeloid LeukemiaPhase 1NCT02588092
Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
A Phase 1 study testing ADCT-301 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by ADC Therapeutics S.A. at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
- What is being tested?
- ADCT-301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 11 sitesUnited States
- Study dates
- 1 Feb 2016to 29 Aug 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Northside Hospital
Atlanta, Georgia, 30342
The University of Chicago Medical Center
Chicago, Illinois, 60647
Duke Cancer Center
Durham, North Carolina, 27710
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Greenville Health System, Institute for Translational Oncology Research
Greenville, South Carolina, 29605
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, 77030
Froedtert Hospital/ Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan Kettering Cancer Center
New York, New York
Swedish Cancer Institute
Seattle, Washington, 98104
University of Washington Medical Center
Seattle, Washington, 98109
About this study
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
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.
Read the 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.
- Being tested
- ADCT-301
- Keywords
- Camidanlumab tesirine
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADCT-301Drug
Also called Camidanlumab tesirine
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: ADCT-301 (dose escalation) | Experimental | 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. Receives: Drug: ADCT-301 |
| Part 2: ADCT-301 (dose expansion) | Experimental | Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee. Receives: Drug: ADCT-301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 to Day 21 (Cycle 1)
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.
Measured: Day 1 to Day 21 (Cycle 1)
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.
Measured: Day 1 to a maximum of 24 weeks (+ 30 days)
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.
Measured: Day 1 to a maximum of 24 weeks (+ 30 days)
Secondary outcomes (27)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: Day 1 to the end of Cycle 2 (6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start1 Feb 2016
- Primary completion29 Aug 2018
- Study completion29 Aug 2018
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aaron Goldberg, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02588092
- Sponsor's protocol ID
- ADCT-301-002
- Status last verified
- Feb 2020
- First submitted
- 13 Aug 2015
- Last updated
- 26 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 32521310
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02588092
- Acronym / sponsor ID
- ADCT-301-002
- Keywords
- Camidanlumab tesirine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 35 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 1 Feb 2016 (actual)
- Primary completion
- 29 Aug 2018 (actual)
- Study completion
- 29 Aug 2018 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Posted 26 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1: ADCT-301 (dose escalation) | Experimental | Drug: ADCT-301Weekly 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. |
| Part 2: ADCT-301 (dose expansion) | Experimental | Drug: ADCT-301Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADCT-301Also: Camidanlumab tesirineIntravenous infusion | Drug | Part 1: ADCT-301 (dose escalation), Part 2: ADCT-301 (dose expansion) |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
Time frame: Day 1 to Day 21 (Cycle 1)
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
Time frame: Day 1 to Day 21 (Cycle 1)
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)
Time frame: Day 1 to a maximum of 24 weeks (+ 30 days)
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)
Time frame: Day 1 to a maximum of 24 weeks (+ 30 days)
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.
27 secondary outcomes
Duration of Response (DOR)
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)
Overall Response Rate (ORR)
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)
Overall Survival (OS)
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)
Number of Participants With Progression Free Survival (PFS)
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)
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
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)
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
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)
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
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)
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
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)
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
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)
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
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)
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
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)
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
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)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
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)
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
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)
Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
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)
Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
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)
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
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)
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
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)
Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
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)
Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
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)
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
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)
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
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)
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
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)
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
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)
Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
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)
Clearance (CL) for ADCT-301 for the QW Dosing Schedule
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)
Number of Participants With Anti-drug Antibody Response (Against ADCT-301)
Time frame: Day 1 to the end of Cycle 2 (6 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32521310Goldberg 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aaron Goldberg, MD principal investigator
Memorial Sloan Kettering Cancer Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ADCT-301 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by ADC Therapeutics S.A. at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) (time frame: Day 1 to Day 21 (Cycle 1)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02588092, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2020.