- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05319249
Natural Killer Cell Immunotherapy in Combination With PARP-inhibition in Acute Myeloid Leukemia (NAKIP-AML)
Natural Killer Cell Immunotherapy in Combination With PARP-inhibition to Overcome NKG2D Mediated Immune Evasion in Acute Myeloid Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Carsten Müller-Tidow, Prof. Dr.
- Phone Number: 8001 +49622156
- Email: carsten.mueller-tidow@med.uni-heidelberg.de
Study Contact Backup
- Name: Richard F. Schlenk, Prof.Dr.
- Phone Number: 6228 +49622156
- Email: richard.schlenk@nct-heidelberg.de
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Patients with confirmed diagnosis of AML according to WHO-2016 (Arber, Orazi et al. 2016) (except acute promyelocytic leukemia) with either de novo AML, AML after preceding myelodysplastic or myeloproliferative syndrome (MDS/MPD), and therapy- related AML (t-AML) after previous cytotoxic therapy or radiation are eligible.
A) Relapsed or Refractory AML with less than 20% bone marrow blasts and less than 20% blasts in peripheral blood.
B) Rising MRD levels (>3 fold) as detected by either molecular genetics or flow cytometry in patients still in hematologic remission.
- Patients who received at least one line of AML therapy. This is defined as either stem cell transplantation or intensive AML therapy or palliative AML therapy containing at least one of the following drugs Azacitidine, Decitabine, Cytarabine, Venetoclax or an FLT3 inhibitor..
- Discontinuation of prior AML treatment before the start of study treatment for at least 107 days for cytotoxic agents and ≥ 53 half-lives for non-cytotoxic / investigational drug treatment preceding the first dose of trial medications.
- Age ≥ 18 years
- ECOG ≤2
Pregnancy and childbearing potential:
- Non-pregnant and non-nursing women of childbearing potential must have a negative serum or urine ß-HCG pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
- Female patients of reproductive age must agree to avoid getting pregnant while on therapy.
- Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin highly effective methods (referring to recommendation of the CTFG) of birth control during study and at least 6 months (women), after end of treatment.
- Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and until 6 months after end of treatment.
- Willingness of patients to adhere to protocol specific requirements and capacity to give written informed consent
- Ability of patient to understand the character and individual consequences of clinical trial
- Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out.
- Suitable donor for NK cell transplantation
Exclusion Criteria:
Patients presenting with any of the following criteria will not be included in the trial:
- Acute promyelocytic leukemia (AML M3)
- AML in which less than 10% of the blasts express the CD34 surface marker expression as analyzed at the local laboratory.
- Known central nervous system manifestation of AML
Uncontrolled or significant cardiovascular disease, including any of the following:
- Heart failure NYHA class 3 or 4
- Left ventricular ejection fraction (LVEF) ≤ 40% by echocardiogram ECHO)
- History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
- History of second (Mobitz II) or third-degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Pregnant or nursing women
- Chronically impaired renal function (creatinine clearance < 30 ml / min)
- Organ dysfunction (e.g. liver, kidney, lung, heart) which in the opinion of the treating physician decreases life expectancy to less than three months.
- Kidney failure with a calculated glomerular filtration rate <30 ml/min or bilirubin >2-fold the upper reference limit of the local laboratory.
- HIV infection and/or active hepatitis B or C infection (active hepatitis B defined by HBs Ag positivity, anti HBs positivity or anti-HBC positivity, active hepatitis C defined by positive virus load).
- Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
- Uncontrolled active infection
- Concurrent malignancies other than AML with an estimated life expectancy of less than two years
- Known hypersensitivity to PARP inhibitors
- Isolated extramedullary manifestation of AML
- Patients < 100 days after allogeneic stem cell transplantation at the time of screening
- Expected non-compliance of patient
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NK cells combined with PARP inhibition
Combination of NK cell therapy and PARP inhibition by Talazoparib after immunosuppression with cyclophosphamide and fludarabine
|
NK cells will be given as a single intravenous infusion.
Other Names:
Subjects will receive treatment with Talazoparib capsules 1 mg/day (4 days) with subsequent intravenous NK cell infusion.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
complete remission (CR/CRi)
Time Frame: Collected at a minimum at baseline, day 28 and latest on day 42
|
response defined as complete remission (CR/CRi) for patients with overt leukemia at time of inclusion and MRD decrease >1log10 for patients with rising MRD at time of inclusion.
|
Collected at a minimum at baseline, day 28 and latest on day 42
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EFS - Event-free survival
Time Frame: EFS is defined as the time of entry into the study to the date of primary refractory disease, or relapse from CR, or CRi, or death from any cause, whichever comes first, assessed up to 42 days.
|
Event-free survival
|
EFS is defined as the time of entry into the study to the date of primary refractory disease, or relapse from CR, or CRi, or death from any cause, whichever comes first, assessed up to 42 days.
|
RFS -Relapse-free survival
Time Frame: Defined as the time from achieving a remission until the date of relapse or death from any cause, whichever comes first, assessed up to 42 days.
|
RFS is defined only for patients achieving CR or CRi
|
Defined as the time from achieving a remission until the date of relapse or death from any cause, whichever comes first, assessed up to 42 days.
|
OS - Overall survival
Time Frame: OS is defined as the time from entry into the trial to the date of death from any cause, assessed up to 42 days.
|
Overall survival
|
OS is defined as the time from entry into the trial to the date of death from any cause, assessed up to 42 days.
|
MRD
Time Frame: Collected at a minimum at baseline, day 28 and latest on day 42
|
Measurable Residual Disease
|
Collected at a minimum at baseline, day 28 and latest on day 42
|
QoL - Quality of life - QLQ-C30
Time Frame: QoL is assessed at baseline and latest on day 42.
|
Validated 30-item self-assessment questionnaire to assess quality of life aspects.
The items are rated on a 4-point Likert scale ranging from 1 (not at all) to 4 (very much) with higher scores meaning a higher level of fatigue.
|
QoL is assessed at baseline and latest on day 42.
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NAKIP_01_2022
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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