Study of AMV564 in Patients With AML

Sponsor

Amphivena Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03144245

Collaborator

(none)

Enrollment

Locations

Arms

43.6

Actual Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first in human, non randomized, open-label, dose escalation study to investigate the safety, tolerability and preliminary efficacy of AMV564.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Biological: AMV564 Combination Product: AMV564 in combination with pembrolizumab	Phase 1

Detailed Description

This study is a first in human, Phase 1, open label, multicenter, dose escalation study with expansion at the RP2D to evaluate the safety, tolerability and preliminary antileukemic activity of AMV564 in patients with relapsed or refractory acute myeloid leukemia (AML).

AMV564 will be given on Days 1-14 of a 4-week cycle, or Days 1-28 of a 6-week cycle,via CIV or subcutaneous administration for 1 or more treatment cycles as monotherapy or in combination with pembrolizumab.

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, First in Human, Open Label, Dose Escalation Study of AMV564, a CD33 x CD3 Tandem Diabody in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Actual Study Start Date :

Mar 20, 2017

Actual Primary Completion Date :

Jul 21, 2020

Actual Study Completion Date :

Nov 5, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMV564 Continuous infusion or subcutaneous dosing of AMV564 at increasing dose levels	Biological: AMV564 AMV564 for administration via continuous intravenous daily infusion or subcutaneous dosing
Experimental: Combination AMV564 Continuous infusion or subcutaneous dosing of AMV564 at increasing dose levels in combination with pembrolizumab	Combination Product: AMV564 in combination with pembrolizumab AMV564 for administration via continuous intravenous daily infusion or subcutaneous dosing.in combination with pembrolizumab given IV every 21 days

Arm

Intervention/Treatment

Experimental: AMV564

Continuous infusion or subcutaneous dosing of AMV564 at increasing dose levels

Biological: AMV564

AMV564 for administration via continuous intravenous daily infusion or subcutaneous dosing

Experimental: Combination AMV564

Continuous infusion or subcutaneous dosing of AMV564 at increasing dose levels in combination with pembrolizumab

Combination Product: AMV564 in combination with pembrolizumab

AMV564 for administration via continuous intravenous daily infusion or subcutaneous dosing.in combination with pembrolizumab given IV every 21 days

Outcome Measures

Primary Outcome Measures

Dose escalation + expansion stage: incidence of all adverse events and serious adverse events (safety and tolerability) [42 months]
Number of participants with adverse events as a measure of safety and tolerability.
Expansion stage: Efficacy - Remission Rate [42 months]
Proportion of participants who achieve complete remission, complete remission with incomplete recovery or partial remission

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 years of age at the time of signing informed consent
Diagnosis of AML according to the World Health Organization (WHO) 2008 criteria
Relapsed or refractory disease meeting the following criteria:

Primary refractory, ie, refractory to induction with a standard intensive anthracycline/cytarabine-based regimen or a non-intensive regimen (e.g., decitabine, azacytidine, low-dose cytarabine) for patients ineligible for an intensive anthracycline/cytarabine-based therapy
First untreated relapse after a first CR lasting less than 12 months or first relapse refractory to salvage therapy regardless of length of first CR; or
Second or later relapse. Relapse is defined as the reappearance of leukemic blasts in the peripheral blood or ≥ 5% leukemic blasts in the bone marrow after prior achievement of a CR or CRi.

OR Patients with newly diagnosed therapy-related AML, AML progressed from antecedent MDS or CMML treated with hypomethylating agents, or de novo AML with MDS-related cytogenetic abnormalities (per 2008 WHO criteria) and who are not candidates for (or decline) intensive remission induction therapy

No more than 3 prior induction/salvage regimens to treat active disease, and no more than 1 prior stem cell transplant. Any number of continuous cycles of therapy with an individual hypomethylating agent count as one induction or salvage regimen.
Blasts at least 5% in bone marrow
Peripheral white blood cell (WBC) count: no upper limit at Screening, but must be < 10 x 109/L on Day 1 prior to treatment; patients with excessive blasts may be treated with hydroxyurea to bring counts down.
Chemistry laboratory parameters within the following range:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x the upper limit of normal (ULN)
Total bilirubin ≤ 1.5x the ULN; patients with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits.
Creatinine clearance > 50 mL/min (measured or calculated by Cockcroft-Gault method)

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients with ECOG score of 2 may be included, after discussion with the Sponsor Medical Monitor, if score is influenced by symptoms attributable to underlying AML disease.
Willing to complete all scheduled visits and assessments at the institution administering therapy
Able to read, understand and provide written informed consent

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study.

History of, or known, central nervous system (CNS) disease involvement, or prior history of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥ 3 drug-related CNS toxicity
Prior allogeneic transplant (dose escalation only)
Prior solid organ transplantation
Treatment with anti-thymocyte globulin (ATG) within 14 days prior to start date
Treatment with any local or systemic antineoplastic therapy or radiation within 14 days prior to the initiation of AMV564 administration (hydroxyurea is exempted if used to reduce total WBC counts)
Clinically significant cardiac disease,
Pulmonary, renal, hepatic, gastrointestinal, neurological or psychiatric disease that would limit compliance with study requirements
Evidence of active, uncontrolled, viral, bacterial, or systemic fungal infection. Prophylactic therapy according to institutional protocols is acceptable.
Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)
Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Patients who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3-year remission include: non-melanoma skin cancer; cervical carcinoma in situ on biopsy or squamous intraepithelial lesion on Papanicolaou (PAP) smear; localized prostate cancer (Gleason score < 6); or resected melanoma in situ.
Major trauma or major surgery within 28 days prior to the initiation of AMV564 treatment
Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the investigator would contraindicate the patient's participation in the study or confound the results of the study.
Ability to become pregnant. However, female patients who have a negative serum or urine pregnancy test before enrollment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom; intrauterine device and condom; diaphragm with spermicidal gel and condom) during the trial and for 90 days afterward (90 days after the end of AMV564 treatment) are considered eligible.
Male patients with partners of childbearing potential.
Pregnant or breastfeeding women
Is a participant or plans to participate in another interventional clinical study, while taking part in this protocol. Participation in an observational study is acceptable.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Northwestern	Chicago	Illinois	United States	60611
3	Johns Hopkins University	Baltimore	Maryland	United States	21287
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	New York Medical College	Hawthorne	New York	United States	10532
6	Weill Cornell Medical College, The New York Presbyterian Hospital	New York	New York	United States	10021
7	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
8	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
9	MD Anderson Cancer Center, The University of Texas	Houston	Texas	United States	70030-4009
10	Fred Hutchinson Cancer Research	Seattle	Washington	United States	98109-1024