Clinical trial NCT02588092: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Keywords: Camidanlumab tesirine
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2015-10-27
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
timeFrame: Day 1 to Day 21 (Cycle 1)
measure: Recommended Dose of ADCT-301 for Part 2
timeFrame: Day 1 to Day 21 (Cycle 1)
measure: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to a maximum of 24 weeks (+ 30 days)
measure: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)
timeFrame: Day 1 to a maximum of 24 weeks (+ 30 days)
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Overall Response Rate (ORR)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Number of Participants With Progression Free Survival (PFS)
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
timeFrame: 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)
measure: Clearance (CL) for ADCT-301 for the QW Dosing Schedule
timeFrame: 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)
measure: Number of Participants With Anti-drug Antibody Response (Against ADCT-301)
timeFrame: Day 1 to the end of Cycle 2 (6 weeks)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Greenville Health System, Institute for Translational Oncology Research
state: South Carolina
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital/ Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Aaron Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.