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Acute Myeloid LeukemiaPhase 1NCT02864290

A Study to Evaluate Escalating Doses of ASP1235 (AGS62P1) Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)

A Phase 1 study testing ASP1235 in people with Acute Myeloid Leukemia, run by Astellas Pharma Global Development, Inc. at 7 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and tolerability of ASP1235 (AGS62P1) given at three dosing schedules (Schedule A, every three weeks [Q3W] or Schedule B, every other week of a 4 week cycle [Q2W] or Schedule C once a week for 3 weeks of a 4 week cycle) in subjects with acute myeloid leukemia (AML)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
ASP1235
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
7 sitesin 2 countries
Study dates
10 Nov 2016to 3 Sep 2020
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Subject has morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) which is relapsed or refractory after failing at least 1 regimen and is not a candidate for established salvage treatment regimens. For expansion cohorts, patients are eligible if they have had ≤ 3 prior lines of therapy. Lines of therapy include initial induction (up to 2 cycles) with consolidation/maintenance, if applicable, and subsequent salvage regimens. Consolidation alone and stem cell transplantation are not counted as lines of therapy.
  • Subject has an Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
  • Subject has adequate renal function with an estimated creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation adjusted for body weight
  • Subject has a total bilirubin ≤ 1.5 x upper limit of normal (ULN), albumin ≥ 2.5 g/d, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
  • Subjects must be competent to comprehend, provide written informed consent, and date an independent ethics committee/institutional review board/research ethics board (IEC/IRB/REB) approved informed consent form
  • A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
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  • Not a woman of childbearing potential (WOCBP) OR
  • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
  • Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study drug administration.
  • A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
  • A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
  • Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.

Who cannot join

  • Subject has a diagnosis of acute promyelocytic leukemia (APL)
  • Subject has preexisting sensory or motor neuropathy Grade ≥ 2 at baseline
  • Subject has received small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, investigational drug, or chemotherapy within 14 days before first dose of study drug, with the exception of hydroxyurea
  • Subject has any Grade ≥ 2 persistent non-hematological toxicity related to allotransplant
  • Subject with Graft vs. Host Disease (GVHD) who is receiving treatment with systemic glucocorticoids > 10 mg/day equivalent of prednisone; however, treatment with low dose glucocorticoids (≤ 10 mg/day equivalent of prednisone) is permitted
  • The use of systemic glucocorticoids in excess of 10 mg/day equivalent of prednisone is permitted provided it is not for the treatment of GVHD (e.g. chronic obstructive pulmonary disease, anti-emetic, infusion reactions). The chronic use of topical, inhaled, and locally injected steroids is permitted
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  • Subject has known current central nervous system (CNS) disease
  • Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
  • Subject has clinical evidence of Disseminated Intravascular Coagulation
  • Subject has known positivity for human immunodeficiency virus
  • Subject has known active hepatitis B (positive hepatitis B surface antigen [HBs Ag]) or C infection. For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible.
  • Subject has an uncontrolled active infection requiring treatment and grade 3 or higher fever 48 hours before the first dose of study drug. Controlled infections (i.e. 3 negative cultures completing antibiotics and/or stable fungal infection in therapy) are allowed provided the subject has a temperature of < 38.3°C within 48 hours of the first dose of study drug.
  • Subject has a known sensitivity to any of the components of the investigational product ASP1235 (AGS62P1):
  • ASP1235 (AGS62P1)
  • L-Histidine base
  • L-Histidine HCl
  • α, α -Trehalose Dihydrate
  • Polysorbate 20
  • Major surgery within 28 days of the first dose of study drug
  • Subject is pregnant or lactating
  • Subject has a condition or situation which may put the subject at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study
  • Subject has any medical, psychiatric, addictive or other disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
  • Subject has ocular condition such as:
  • Active infection or corneal ulcer
  • Monocularity
  • History of corneal transplantation
  • Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration)
  • Uncontrolled glaucoma (topical medications allowed)
  • Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, macular degeneration) requiring surgery, laser treatment, or intravitreal injections
  • Papilledema or other active optic nerve disorder

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

United States6 sites

  • Site US00003

    Baltimore, Maryland, 21287

  • Site US00007

    Boston, Massachusetts, 02114

  • Site US00009

    Boston, Massachusetts, 02114

  • Site US00006

    Duarte, California, 91010

  • Site US00001

    Houston, Texas, 77030

  • Site US00004

    New York, New York, 10016

Other trials in United States

Canada1 site

  • Site CA00010

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase 1 Study Evaluating Safety, Tolerability, and Pharmacokinetics of Escalating Doses of ASP1235 (AGS62P1) Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)

The purpose of this study is to evaluate the safety and tolerability of ASP1235 (AGS62P1) given at three dosing schedules (Schedule A, every three weeks [Q3W] or Schedule B, every other week of a 4 week cycle [Q2W] or Schedule C once a week for 3 weeks of a 4 week cycle) in subjects with acute myeloid leukemia (AML) and determine the maximum tolerated dose (MTD). In addition, this study will assess the pharmacokinetics (PK), the immunogenicity and the anti-leukemic activity of ASP1235 (AGS62P1).

Being tested
ASP1235
Keywords
AML, Pharmacokinetics of ASP1235 (AGS62P1), ASP1235, Acute Myeloid Leukemia, ASP1235 (AGS62P1)
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ASP1235Drug

    Also called AGS62P1

    intravenous (IV) infusion

Study groups in NCT02864290
Study groupRoleWhat they receive
Dose Escalation of ASP1235 (AGS62P1) Schedule AExperimentalSubjects will receive ASP1235 (AGS62P1) as an intravenous infusion once every three weeks (Q3W) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose. A cycle is 21 days.
Receives: Drug: ASP1235
Dose Escalation of ASP1235 (AGS62P1) Schedule BExperimentalSubjects will receive ASP1235 (AGS62P1) as an intravenous infusion every other week of a 4-week cycle (Q2W) to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose. A cycle is 28 days.
Receives: Drug: ASP1235
Dose Expansion of ASP1235 (AGS62P1) Schedule AExperimentalOnce the maximum tolerated dose (MTD) or recommended Phase 2 dose has been determined, an expansion cohort of up to 25 subjects may be enrolled. Subjects will receive ASP1235 (AGS62P1) as an intravenous infusion once every three weeks (Q3W).
Receives: Drug: ASP1235
Dose Expansion of ASP1235 (AGS62P1) Schedule BExperimentalOnce the maximum tolerated dose (MTD) or recommended Phase 2 dose has been determined, an expansion cohort of up to 25 subjects may be enrolled. Subjects will receive ASP1235 (AGS62P1) as an intravenous infusion every other week of a 4-week cycle (Q2W).
Receives: Drug: ASP1235
Dose Escalation of ASP1235 (AGS62P1) Schedule CExperimentalSubjects will receive ASP1235 (AGS62P1) as an intravenous infusion once weekly for three weeks of a 4-week cycle to determine the MTD or recommended Phase 2 dose. A cycle is 28 days.
Receives: Drug: ASP1235
Dose Expansion of ASP1235 (AGS62P1) Schedule CExperimentalOnce the MTD or recommended Phase 2 dose has been determined, an expansion cohort of up to 25 subjects may be enrolled. Subjects will receive ASP1235 (AGS62P1) as an intravenous infusion once weekly for three weeks pf a 4-week cycle.
Receives: Drug: ASP1235

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and nature of adverse events

    AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) grading scale, version 4.03 (National Institutes of Health, 2010).

    Measured: up to 30 months

Secondary outcomes (49)

  1. Incidence of antidrug antibody (ADA) formation to the fully human monoclonal antibody (AGS62P) and antibody-conjugate (ASP1235 [AGS62P1])

    Measured: up to 46 months

  2. Complete response (CR)

    Measured: up to 46 months

  3. Composite complete remission (CRc) rate

    Measured: up to 46 months

  4. Best response rate

    Measured: up to 46 months

  5. Duration of remission

    Measured: up to 46 months

  6. Duration of response

    Measured: up to 46 months

  7. Morphologic leukemia free state (MLFS) rate

    Measured: up to 30 months

  8. Concentration at the end of infusion (CEOI) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  9. Concentration at the end of infusion (CEOI) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  10. Concentration at the end of infusion (CEOI) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  11. Maximum observed concentration (Cmax) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  12. Maximum observed concentration (Cmax) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  13. Maximum observed concentration (Cmax) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  14. Time to maximum concentration (Tmax) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  15. Time to maximum concentration (Tmax) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  16. Time to maximum concentration (Tmax) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  17. Partial area under the serum concentration-time curve (AUC) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  18. Partial area under the serum concentration-time curve (AUC) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  19. Partial area under the serum concentration-time curve (AUC) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  20. Terminal or apparent terminal half-life (t1/2) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  21. Terminal or apparent terminal half-life (t1/2) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  22. Terminal or apparent terminal half-life (t1/2) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  23. Systemic clearance (CL) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  24. Systemic clearance (CL) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  25. Systemic clearance (CL) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  26. Volume of distribution at steady state (Vss) of total antibody (TAb) in dose escalation part

    Measured: up to an average of 30 months

  27. Volume of distribution at steady state (Vss) of antibody drug conjugate (ADC) in dose escalation part

    Measured: up to an average of 30 months

  28. Volume of distribution at steady state (Vss) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose escalation part

    Measured: up to an average of 30 months

  29. Concentration at the end of infusion (CEOI) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  30. Concentration at the end of infusion (CEOI) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  31. Concentration at the end of infusion (CEOI) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  32. Maximum observed concentration (Cmax) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  33. Maximum observed concentration (Cmax) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  34. Maximum observed concentration (Cmax) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  35. Time to maximum concentration (Tmax) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  36. Time to maximum concentration (Tmax) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  37. Time to maximum concentration (Tmax) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  38. Partial area under the serum concentration-time curve (AUC) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  39. Partial area under the serum concentration-time curve (AUC) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  40. Partial area under the serum concentration-time curve (AUC) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  41. Terminal or apparent terminal half-life (t1/2) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  42. Terminal or apparent terminal half-life (t1/2) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  43. Terminal or apparent terminal half-life (t1/2) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  44. Systemic clearance (CL) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  45. Systemic clearance (CL) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  46. Systemic clearance (CL) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

  47. Volume of distribution at steady state (Vss) of total antibody (TAb) in dose expansion part

    Measured: up to an average of 30 months

  48. Volume of distribution at steady state (Vss) of antibody drug conjugate (ADC) in dose expansion part

    Measured: up to an average of 30 months

  49. Volume of distribution at steady state (Vss) of metabolite para-acetyl phenylalanine attached to the microtubule disrupting agent linked to linker 30 (pAF-AGL-0185-30) in dose expansion part

    Measured: up to an average of 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2016 (estimated)
  2. Study start10 Nov 2016
  3. Primary completion3 Sep 2020
  4. Study completion3 Sep 2020

Why it stopped: Study was terminated due to lack of efficacy.

Resources

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
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02864290
Sponsor's protocol ID
1235-CL-0101
Other IDs
AGS62P1-16-1
Status last verified
Oct 2024
First submitted
30 Jun 2016
Last updated
23 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Publications

  • Al Malki MM, Minden MD, Rich ES, Hill JE, Gill SC, Fan A, Fredericks CE, Fathi AT, Abdul-Hay M. Safety, tolerability, and pharmacokinetics of ASP1235 in relapsed or refractory acute myeloid leukemia: A phase 1 study. Leuk Res. 2025 May;152:107690. doi: 10.1016/j.leukres.2025.107690. Epub 2025 Apr 2.

    PubMed 40209615

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ASP1235 in people with Acute Myeloid Leukemia, run by Astellas Pharma Global Development, Inc. at 7 sites in 2 countries.

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 13 inclusion and 30 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 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Canada. 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?

The study was stopped early (reason given: Study was terminated due to lack of efficacy.). Results are not available in the source record.

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?

Incidence and nature of adverse events (time frame: up to 30 months). 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 NCT02864290, 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 23 Oct 2024.

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