Pharmacoscopy-guided Clinical Standard-of-care in r/r AML (RAPID-01)

Pharmacoscopy-guided Clinical Standard-of-care in Relapsed/Refractory Acute Myeloid Leukemia, a Randomized Phase-2 Clinical Trial

With an overall survival of below 12 months, the outcome of relapsed/refractory AML (RR AML) is poor, making it a critical challenge to identify effective therapies at this stage. The RAPID-01 trial aims to show for the first time in a randomized and controlled clinical trial that Pharmacoscopy (PCY), a functional precision medicine platform, helps improve clinical standard-of-care treatment selection for patients suffering from relapsed/refractory AML.

Study Overview

• Status: Not yet recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Diagnostic test: Pharmacoscopy; Drug: Clinical standard-of-care (physician's choice)

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Berend Snijder, PhD; Phone Number: +41 44 633 71 49; Email: bsnijder@ethz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Patient with refractory or relapsed AML according to ELN2022 criteria.
• Age 18-70 years.
• Considered to be eligible for intensive chemotherapy.
• Written informed consent.

Exclusion criteria

• Acute promyelocytic leukemia (APL) with PML-RARA or one of the other pathognomonic variant fusion genes/chromosome translocations.
• Blast crisis after chronic myeloid leukemia (CML).
• Considered not eligible for intensive chemotherapy.
• Condition of the patient does not allow to wait for PCY results (patient requires immediate treatment).
• PCY not working / patient sample did not pass the QC steps of PCY.
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the principal investigator may interfere with the project or affect patient compliance.
• Legal incompetence or Subjects lacking capacity to provide informed consent.
• Participation in a clinical trial with an investigational drug within the 30 days preceding and during the present investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm: Pharmacoscopy-guided clinical standard-of-care; Patients in the PCY-guided treatment arm will receive one of the clinical standard-of-care treatments suggested by their own PCY results, and confirmed by the treating physician.	Diagnostic test: Pharmacoscopy; Pharmacoscopy (PCY) is an image-based ex vivo drug testing platform developed by the Snijder lab at the ETH Zurich. PCY measures in the drug response of patient cells from small biopsies using automated microscopy and single-cell image analysis. PCY prioritizes treatments based on their specific efficacy against AML cells, while minimizing toxicity to healthy (non-malignant) cells in the patient biopsy.
Active Comparator: Control arm; Patients in the control arm will be treated with clinical standard-of-care therapy for RR AML selected by the physician (physician's choice).	Drug: Clinical standard-of-care (physician's choice); Clinical standard-of-care therapy for RR AML selected by the physician (physician's choice).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response (CR) rate at day 28	day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite response rate (CR+CRh+CRi) at day 28	day 28
Rate of patients bridged to allogeneic hematopoietic stem cell transplantation within 3 months post-treatment initiation	3 months
Treatment-related mortality within 3 months post-treatment initiation	3 months

Collaborators and Investigators

• Sponsor: ETH Zurich
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Alexandre Theocharides, MD PhD, University of Zurich

Publications and helpful links

General Publications

• Snijder B, Vladimer GI, Krall N, Miura K, Schmolke AS, Kornauth C, Lopez de la Fuente O, Choi HS, van der Kouwe E, Gultekin S, Kazianka L, Bigenzahn JW, Hoermann G, Prutsch N, Merkel O, Ringler A, Sabler M, Jeryczynski G, Mayerhoefer ME, Simonitsch-Klupp I, Ocko K, Felberbauer F, Mullauer L, Prager GW, Korkmaz B, Kenner L, Sperr WR, Kralovics R, Gisslinger H, Valent P, Kubicek S, Jager U, Staber PB, Superti-Furga G. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 2017 Dec;4(12):e595-e606. doi: 10.1016/S2352-3026(17)30208-9. Epub 2017 Nov 15.
• Kornauth C, Pemovska T, Vladimer GI, Bayer G, Bergmann M, Eder S, Eichner R, Erl M, Esterbauer H, Exner R, Felsleitner-Hauer V, Forte M, Gaiger A, Geissler K, Greinix HT, Gstottner W, Hacker M, Hartmann BL, Hauswirth AW, Heinemann T, Heintel D, Hoda MA, Hopfinger G, Jaeger U, Kazianka L, Kenner L, Kiesewetter B, Krall N, Krajnik G, Kubicek S, Le T, Lubowitzki S, Mayerhoefer ME, Menschel E, Merkel O, Miura K, Mullauer L, Neumeister P, Noesslinger T, Ocko K, Ohler L, Panny M, Pichler A, Porpaczy E, Prager GW, Raderer M, Ristl R, Ruckser R, Salamon J, Schiefer AI, Schmolke AS, Schwarzinger I, Selzer E, Sillaber C, Skrabs C, Sperr WR, Srndic I, Thalhammer R, Valent P, van der Kouwe E, Vanura K, Vogt S, Waldstein C, Wolf D, Zielinski CC, Zojer N, Simonitsch-Klupp I, Superti-Furga G, Snijder B, Staber PB. Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders. Cancer Discov. 2022 Feb;12(2):372-387. doi: 10.1158/2159-8290.CD-21-0538. Epub 2021 Oct 11.
• Schmid JA, Festl Y, Severin Y, Bacher U, Kronig MN, Snijder B, Pabst T. Efficacy and feasibility of pharmacoscopy-guided treatment for acute myeloid leukemia patients who have exhausted all registered therapeutic options. Haematologica. 2023 Jul 13. doi: 10.3324/haematol.2023.283224. Online ahead of print.

Helpful Links

• Snijder Lab website

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacoscopy; Functional precision medicine; relapsed / refractory AML
• Other Study ID Numbers: RAPID-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified patient data will be made available upon publication of the study results in a peer-reviewed internationally recognized journal.
• IPD Sharing Time Frame: De-identified patient data will be made available upon publication of the study results in a peer-reviewed internationally recognized journal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No