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

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ClinicalTrials.gov Identifier: NCT02864290
Recruitment Status : Recruiting
First Posted : August 12, 2016
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief 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) 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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: ASP1235 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 10, 2016
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2024


Arm Intervention/treatment
Experimental: Dose Escalation of ASP1235 (AGS62P1) Schedule A
Subjects 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.
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1

Experimental: Dose Escalation of ASP1235 (AGS62P1) Schedule B
Subjects 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.
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1

Experimental: Dose Expansion of ASP1235 (AGS62P1) Schedule A
Once 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).
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1

Experimental: Dose Expansion of ASP1235 (AGS62P1) Schedule B
Once 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).
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1

Experimental: Dose Escalation of ASP1235 (AGS62P1) Schedule C
Subjects 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.
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1

Experimental: Dose Expansion of ASP1235 (AGS62P1) Schedule C
Once 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.
Drug: ASP1235
intravenous (IV) infusion
Other Name: AGS62P1




Primary Outcome Measures :
  1. Incidence and nature of adverse events [ Time Frame: up to 30 months ]
    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).


Secondary Outcome Measures :
  1. Incidence of antidrug antibody (ADA) formation to the fully human monoclonal antibody (AGS62P) and antibody-conjugate (ASP1235 [AGS62P1]) [ Time Frame: up to 54 months ]
  2. Complete response (CR) [ Time Frame: up to 54 months ]
  3. Composite complete remission (CRc) rate [ Time Frame: up to 54 months ]
  4. Best response rate [ Time Frame: up to 54 months ]
  5. Duration of remission [ Time Frame: up to 54 months ]
  6. Duration of response [ Time Frame: up to 54 months ]
  7. Morphologic leukemia free state (MLFS) rate [ Time Frame: up to 30 months ]
  8. Concentration at the end of infusion (CEOI) of total antibody (TAb) in dose escalation part [ Time Frame: up to an average of 30 months ]
  9. Concentration at the end of infusion (CEOI) of antibody drug conjugate (ADC) in dose escalation part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  11. Maximum observed concentration (Cmax) of total antibody (TAb) in dose escalation part [ Time Frame: up to an average of 30 months ]
  12. Maximum observed concentration (Cmax) of antibody drug conjugate (ADC) in dose escalation part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  14. Time to maximum concentration (Tmax) of total antibody (TAb) in dose escalation part [ Time Frame: up to an average of 30 months ]
  15. Time to maximum concentration (Tmax) of antibody drug conjugate (ADC) in dose escalation part [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  20. Terminal or apparent terminal half-life (t1/2) of total antibody (TAb) in dose escalation part [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  23. Systemic clearance (CL) of total antibody (TAb) in dose escalation part [ Time Frame: up to an average of 30 months ]
  24. Systemic clearance (CL) of antibody drug conjugate (ADC) in dose escalation part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  26. Volume of distribution at steady state (Vss) of total antibody (TAb) in dose escalation part [ Time Frame: up to an average of 30 months ]
  27. Volume of distribution at steady state (Vss) of antibody drug conjugate (ADC) in dose escalation part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  29. Concentration at the end of infusion (CEOI) of total antibody (TAb) in dose expansion part [ Time Frame: up to an average of 30 months ]
  30. Concentration at the end of infusion (CEOI) of antibody drug conjugate (ADC) in dose expansion part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  32. Maximum observed concentration (Cmax) of total antibody (TAb) in dose expansion part [ Time Frame: up to an average of 30 months ]
  33. Maximum observed concentration (Cmax) of antibody drug conjugate (ADC) in dose expansion part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  35. Time to maximum concentration (Tmax) of total antibody (TAb) in dose expansion part [ Time Frame: up to an average of 30 months ]
  36. Time to maximum concentration (Tmax) of antibody drug conjugate (ADC) in dose expansion part [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  41. Terminal or apparent terminal half-life (t1/2) of total antibody (TAb) in dose expansion part [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  44. Systemic clearance (CL) of total antibody (TAb) in dose expansion part [ Time Frame: up to an average of 30 months ]
  45. Systemic clearance (CL) of antibody drug conjugate (ADC) in dose expansion part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]
  47. Volume of distribution at steady state (Vss) of total antibody (TAb) in dose expansion part [ Time Frame: up to an average of 30 months ]
  48. Volume of distribution at steady state (Vss) of antibody drug conjugate (ADC) in dose expansion part [ Time Frame: 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 [ Time Frame: up to an average of 30 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • 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.

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02864290


Contacts
Contact: Astellas Pharma Global Development, Inc. 800-888-7704 astellas.registration@astellas.com

Locations
United States, California
Site US00006 Recruiting
Duarte, California, United States, 91010
United States, Maryland
Site US00003 Active, not recruiting
Baltimore, Maryland, United States, 21287
United States, New York
Site US00004 Recruiting
New York, New York, United States, 10016
United States, Texas
Site US00001 Recruiting
Houston, Texas, United States, 77030
Canada, Ontario
Site CA00010 Active, not recruiting
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Associate Medical Officer Astellas Pharma Global Development, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02864290     History of Changes
Other Study ID Numbers: 1235-CL-0101
AGS62P1-16-1 ( Other Identifier: Astellas Pharma Global Development, Inc. )
First Posted: August 12, 2016    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
AML
Pharmacokinetics of ASP1235 (AGS62P1)
ASP1235
Acute Myeloid Leukemia
ASP1235 (AGS62P1)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms