Extended Analysis for Leukemia/Lymphoma Treatment

NCT03096821 | Completed DMC

• 2 other identifiers: EXALT1.11830/2015
• Study Type: observational
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with relapsed/ refractory acute leukemia and relapsed/ refractory aggressive lymphoma harboring an activating genetic alteration (gene mutation, gene fusion) or drug-able biomarker / activated signal transduction pathway and resistant to any approved treatment modality will be eligible for this study. The investigators aim to combine DNA sequencing-based molecular profiling with an ex vivo high-throughput drug screening strategy. For the latter method, viable cells are obtained from the individual patient's lymphoma or leukemia in order to determine i)the expression of relevant therapeutic target molecules and ii)the ex vivo response of the patient's cancer cells to a panel of agents with anticancer activity. In addition, analysis of tumor stroma cells will provide information about the differential target expression and cellular sensitivity aiming at the evaluation of a therapeutic safety window. Thereby, biological material will have to be accessed within 4 weeks before onset of individualized treatment (real-time biopsy). Bioinformatic data-management based on a Bayesian statistical approach will support individualized treatment decisions in this controlled clinical approach.

Conditions

Relapsed Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  To compare progression-free survival using a treatment regimen selected by molecular profiling with progression-free survival for the most recent regimen the patient has progressed on. The treatment concept is deemed for clinical benefit for the individual patient who has a PSF ratio (PSF on molecular profiling-based therapy/PSF on prior therapy) of ≥ 1.3. For this purpose we will reject the null hypothesis, which is defined as follows: ≤ 15% of patients would have a PFS ratio of ≥ 1.3. Thus, the individual patient is his own control. For tumor types with high numbers of patients per cohort, the overall response rate (ORR) will be evaluated.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (1)

• overall response rate

  4 months

Study Arms (1)

ngFDS selected treatment

Treatment with commercially available treatments (per package insert instructions) chosen via next-generation functional drug screening (ngFDS).

Drug: ngFDS selected treatment

Interventions

ngFDS selected treatment DRUG

Treatment based on next-generation functional drug screening (ngFDS). Treatment with commercially available treatments (per package insert instructions) selected by functional drug screening. For drug screening tumor cells from bone marrow aspirates, peripheral blood, pleural effusion, or excised lymph node samples are purified over Ficoll gradient (bone marrow, peripheral blood, pleural effusion) (GE healthcare) or homogenized and filtered (lymph tissue).

Also known as: Treatment based on ngFDS

ngFDS selected treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with relapsed or refractory aggressive hematological malignancy lacking further standard treatment.

You may qualify if:

• There are no further standard treatments available for the patient;
• The patient has undergone at least two lines of previous therapy;
• Cancer cell-containing biopsies are obtainable;
• Informed consent from the patient was given;
• candidate treatments identified by ngFDS are clinically available and considered safe given the patient health state.

You may not qualify if:

• Presence of further treatment options, as defined by NCCN guidelines or Austrian guidelines representing a possible further treatment-related response by conventional therapies according to generally accepted medical evidence.
• No fresh and viable tumor material available.
• Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia.
• Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
• A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
• A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Uncontrolled medical conditions (i.e, diabetes mellitus, hypertension, etc), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
• Pregnant or lactating females.
• History of alcohol or drug abuse within 6 months prior to screening.
• No informed consent available.

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Vienna

Vienna, 1090, Austria

Location

Related Publications (2)

• Liebers N, Bruch PM, Terzer T, Hernandez-Hernandez M, Paramasivam N, Fitzgerald D, Altmann H, Roider T, Kolb C, Knoll M, Lenze A, Platzbecker U, Rollig C, Baldus C, Serve H, Bornhauser M, Hubschmann D, Muller-Tidow C, Stolzel F, Huber W, Benner A, Zenz T, Lu J, Dietrich S. Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial. Nat Cancer. 2023 Dec;4(12):1648-1659. doi: 10.1038/s43018-023-00645-5. Epub 2023 Oct 2.

  PMID: 37783805 DERIVED

• 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.

  PMID: 29153976 DERIVED

Related Links

• Publication of Interimsanalysis

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Philipp B Staber, MD, PhD

  Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.

Study Record Dates

• First Submitted: March 18, 2017
• First Posted: March 30, 2017
• Study Start: September 1, 2015
• Primary Completion: January 30, 2020
• Study Completion: January 30, 2020
• Last Updated: February 24, 2021

Record last verified: 2021-02

Locations

AU (1)