Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05662904
Other study ID # 2022-002
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date December 2023
Est. completion date February 2025

Study information

Verified date December 2022
Source German Cancer Research Center
Contact Tim Sauer, Dr. med.
Phone +49 6221 56 38010
Email tim.sauer@med.uni-heidelberg.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

CRISPR/Cas9-mediated inactivation of CD33 in hematopoietic stem cells (HSC) may broaden the therapeutic index of CD33-directed immunotherapy for patients with AML by rendering healthy hematopoietic stem and progenitor cells (HSPC) resistant to escalating doses and/or shorter dosing intervals of the CD33-specific antibody-drug conjugate (ADC) Gemtuzumab-ozogamicin (GO). In this proof of concept trial, we will develop a platform for genome editing of CD34+ HSC and demonstrate the feasibility, safety and efficacy of this approach for targeted therapy of AML. Upon implementation, the platform shall be used for innovative clinical trials in diverse types of cancer. Outside of leukemias, autologous HSC could be used to ease the procedure. 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. Upon HSC engraftment, patients will be treated with escalating doses of the anti-CD33 antibodydrug conjugate Gemtuzumab-Ozogamicin (GO). A conditioning regimen containing GO (d-14, d-11, d-8),Fludarabine 30 mg/m2 (d-6 to d-3) and Melphalan 140mg/m2 (d-2) is used prior to transplantation. The clinical trial will be conducted at two trial sites in the University Hospitals in Heidelberg and Dresden. 25 patients will be assessed for eligibility and 12 patients will be allocated into the trial.


Recruitment information / eligibility

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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Donor-derived CD34+ HSC with CRISPR/Cas9-mediated CD33 deletion
CD33-deleted CD34+ hematopoietic stem cells derived from the initially matched family donor
Drug:
Gemtuzumab Ozogamicin
Intrapatient intra-individual dose escalation Level 0: GO day 1 Level 1: GO day 1, day 4 Level 2: GO day 1, day 4, day 7 with repetition after 21 to 28 days up to 84 days.

Locations

Country Name City State
Germany University Hospital Dresden, Department of Medicine I Dresden
Germany University Hospital Heidelberg, Internal Medicine V Heidelberg

Sponsors (3)

Lead Sponsor Collaborator
German Cancer Research Center University Hospital Dresden, University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

Outcome

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
See also
  Status Clinical Trial Phase
Terminated NCT03541369 - Safety, Tolerability, PK, PD, and Efficacy of AMG 427 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia Phase 1
Recruiting NCT05143996 - CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Phase 1
Completed NCT02626338 - Pilot Study of Crenolanib Combined With Standard Salvage Chemotherapy in Subjects With R/R AML Phase 1/Phase 2
Recruiting NCT06049667 - A Phase 1 Clinical Trail of NTQ2494 Tablets in Patients With Advanced Hematological Malignancies Phase 1