Relapsed/Refractory Acute Myeloid Leukemia (AML) Clinical Trial
— GALAXY33Official title:
Genetic Ablation of CD33 in Hematopoietic Stem Cells to Broaden the Therapeutic Index of CD33-directed Immunotherapy in Patients With Acute Myeloid Leukemia (AML)
The study "GALAXY33" is an open-label, prospective, nonrandomized, one arm phase I clinical trial in which patients with relapsed AML after allogeneic hematopoietic stem cell transplantation will be transplanted with CD33-deleted CD34+ HSC derived from the initially matched family donor.
Status | Not yet recruiting |
Enrollment | 12 |
Est. completion date | February 2025 |
Est. primary completion date | February 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Key Inclusion Criteria: - confirmed AML according to the WHO classification - relapsed disease after allo-SCT from an HLA-identical family donor (= 2 months after allo-SCT at time of inclusion) - = 29% of bone marrow blasts as detected by cytomorphology or immunohistochemistry - age = 18 years - confirmed CD33 expression on leukemic blasts at current relapse (as detected by flow cytometry) - adequate organ function: - Renal function defined as: serum creatinine of = 2x ULN or eGFR = 30 mL/min/1.73 m2 - Liver function defined as: - ALT = 3 times the ULN for the respective age - Bilirubin = 2.0 mg/dl with the exception of patients with hyperbilirubinemia explained by Gilbert-Meulengracht syndrome (may be included if total bilirubin is = 3.0 x ULN and direct bilirubin = 1.5 x ULN) or extrahepatic disease (e.g. chronic hemolytic anemia) - Minimum level of pulmonary reserve defined as = grade 1 dyspnea and pulse oxygenation > 90% on room air - Hemodynamic stability and LVEF = 40% as confirmed by echocardiogram - Absolute lymphocyte count (ALC) = 100/mm3 Key Exclusion Criteria: - ECOG performance status >2 - Confirmed CNS involvement - Acute or chronic Graft versus Host disease (GvHD) - Availability of other curative standard treatment options - Prior treatment with GO - Prior hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) - Uncontrolled active hepatitis B or C - HIV-positivity - Uncontrolled bacterial, viral or fungal infection - Participation in another clinical trial at the time of screening - Organ dysfunction (liver, kidney, lung, heart) that is a contraindication for conditioning therapy - Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure NYHA III-IV, uncontrolled diabetes mellitus, uncontrolled hyperlipidemia) - Unstable angina and/or myocardial infarction within 3 months prior to screening - Pregnant or nursing (lactating) women |
Country | Name | City | State |
---|---|---|---|
Germany | University Hospital Dresden, Department of Medicine I | Dresden | |
Germany | University Hospital Heidelberg, Internal Medicine V | Heidelberg |
Lead Sponsor | Collaborator |
---|---|
German Cancer Research Center | University Hospital Dresden, University Hospital Heidelberg |
Germany,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | engraftement of gene edited CD34+HSC | successful engraftement of gene edited CD34+HSC in the bone marrow | on day 28 | |
Primary | dose-limiting toxicity | dose-limiting toxicity (DLT) of Gemtuzumab-Ozogamicin | until EOS (day 90) | |
Primary | toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | frequency and grade of AEs with gene-edited HSC transplantation | until EOS (day 90) | |
Secondary | Anti-tumor efficacy of study treatment in patients with dCD33+ relapsed AML after allo-SCT | overall response rate (ORR), complete response (CR), partial response (PR)) at day 90 (EOS) after last GO application) | until EOS (day 90) | |
Secondary | Time to response | Time to response (at least partial response) after the last GO application | until EOS (day 90) | |
Secondary | Overall response | Duration of overall response (DOR) after the last GO application | until EOS (day 90) | |
Secondary | Progression-free survival | Progression-free survival (PFS) after the last GO application | until EOS (day 90) | |
Secondary | Overall survival | Overall survival (OS) after the last GO application | until EOS (day 90) | |
Secondary | Number of circulating gene edited cells | Number of circulating gene edited cells in the bone marrow and peripheral blood as determined by flow cytometry | at screening and days 14, 28, 56, 90 |
Status | Clinical Trial | Phase | |
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