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Acute Myeloid LeukemiaPhase 1/2NAKIP-AMLNCT05319249

Natural Killer Cell Immunotherapy in Combination With PARP-inhibition in Acute Myeloid Leukemia

A Phase 1/2 study testing NK cells and Talazoparib 1 MG [Talzenna] in people with Acute Myeloid Leukemia, run by German Cancer Research Center.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Therapy resistance remains the major obstacle to cure in many types of cancer. In particular in leukemia, therapy resistance depends on leukemic stem cells (LSC) that exhibit inherent therapy resistance to multiple drugs and contribute to overt leukemic relapse. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
NK cells and Talazoparib 1 MG [Talzenna]
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
No sites listed yet
Study dates
Jun 2024to Jun 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Relapsed or Refractory AML with less than 20% bone marrow blasts and less than 20% blasts in peripheral blood.
  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Carsten Müller-Tidow, Prof. Dr. contact

+49622156 ext. 8001

carsten.mueller-tidow@med.uni-heidelberg.de

Richard F. Schlenk, Prof.Dr. contact

+49622156 ext. 6228

richard.schlenk@nct-heidelberg.de

About this study

Official title: Natural Killer Cell Immunotherapy in Combination With PARP-inhibition to Overcome NKG2D Mediated Immune Evasion in Acute Myeloid Leukemia

Therapy resistance remains the major obstacle to cure in many types of cancer. In particular in leukemia, therapy resistance depends on leukemic stem cells (LSC) that exhibit inherent therapy resistance to multiple drugs and contribute to overt leukemic relapse. Cellular therapies alone or in combination with other targeted or chemotherapeutic approaches can overcome drug mediated therapy resistance and induce long lasting remissions. Several trials have shown that adoptive transfer of allogeneic NK cells can induce clinical remission in patients with myeloid malignancies. In addition, the antileukemic efficacy of alloreactive NK cells has been shown to facilitate cure after T cell depleted haploidentical stem cell transplantation. Recently, it was demonstrated that absence of NKGD2 ligand expression on leukemic stem cells determines therapy resistance and immune escape towards NK cells in AML. PARP1 inhibitors can induce re-expression of NKG2D ligands. This phase I/II clinical trial will evaluate the combination of NK cell therapy and PARP inhibition by Talazoparib in patients with poor prognosis AML as characterized by Minimal Residual Disease (MRD) or overt relapse with less than 20% bone marrow blasts. The hypothesis that allogeneic NK cell therapy combined with PARP inhibition will increase the response rate (CR/CRi for relapsed/ refractory patients and MRD-response for MRD positive patients) from 35% to 60% will be tested. The co-primary endpoints are i) response to treatment defined as complete remission (CR) for patients with overt leukemia at time of inclusion and MRD decrease >1log10 for patients with rising MRD at time of inclusion as well as ii) safety and feasibility of the protocol. Key secondary endpoints are event free survival and overall survival. Two cohorts will be assessed independently: patients with i) overt leukemia and ii) patients with rising MRD at time of inclusion. Safety and feasibility will be analyzed continuously during the entire trial. The NAKIP-AML trial will analyze efficacy and feasibility of NK cell transplantation together with PARP1 inhibition.

Being tested
NK cells, Talazoparib 1 MG [Talzenna]
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NK cellsBiological

    Also called Haploidentical human allogeneic NK cells

    NK cells will be given as a single intravenous infusion.

  • Talazoparib 1 MG [Talzenna]Drug

    Also called Talzenna

    Subjects will receive treatment with Talazoparib capsules 1 mg/day (4 days) with subsequent intravenous NK cell infusion.

Study groups in NCT05319249
Study groupRoleWhat they receive
NK cells combined with PARP inhibitionExperimentalCombination of NK cell therapy and PARP inhibition by Talazoparib after immunosuppression with cyclophosphamide and fludarabine
Receives: Biological: NK cells; Drug: Talazoparib 1 MG [Talzenna]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. complete remission (CR/CRi)

    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.

    Measured: Collected at a minimum at baseline, day 28 and latest on day 42

Secondary outcomes (5)

  1. EFS - Event-free survival

    Event-free survival

    Measured: 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.

  2. RFS -Relapse-free survival

    RFS is defined only for patients achieving CR or CRi

    Measured: 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.

  3. OS - Overall survival

    Overall survival

    Measured: OS is defined as the time from entry into the trial to the date of death from any cause, assessed up to 42 days.

  4. MRD

    Measurable Residual Disease

    Measured: Collected at a minimum at baseline, day 28 and latest on day 42

  5. QoL - Quality of life - QLQ-C30

    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.

    Measured: QoL is assessed at baseline and latest on day 42.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2022
  2. Study startJun 2024 (estimated)
  3. Primary completionJun 2028 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05319249
Sponsor's protocol ID
NAKIP_01_2022
Acronym
NAKIP-AML
Status last verified
Apr 2024
First submitted
21 Mar 2022
Last updated
5 Apr 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NK cells and Talazoparib 1 MG [Talzenna] in people with Acute Myeloid Leukemia, run by German Cancer Research Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 5 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Carsten Müller-Tidow, Prof. Dr. (+49622156 ext. 8001, carsten.mueller-tidow@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

complete remission (CR/CRi) (time frame: Collected at a minimum at baseline, day 28 and latest on day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05319249.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2024.

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