Leukemia, Myeloid, AcutePhase 1NCT02781467
A Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (rhIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML)
A Phase 1 study testing PNK-007, Cyclophosphamide and Fludarabine in people with Leukemia, Myeloid, Acute, run by Celularity Incorporated at 7 sites in United States.
Trial summary
This study will find the highest acceptable treatment dose of cord blood, culture expanded natural killer (NK) cells, a kind of immune cell, in patients with relapsed and/or refractory acute myeloid leukemia. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- PNK-007, Cyclophosphamide and Fludarabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 7 sitesUnited States
- Study dates
- 11 Jul 2016to 7 Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subject has an eligible disease:
- Primary Acute myeloid leukemia (AML) induction failure: no Complete Remission (CR) after 2 or more induction attempts or
- Relapsed AML: not in CR after 1 or more cycles of standard re-induction chemotherapy
- For relapsed subjects > 60 years of age, the 1 cycle of standard re-induction chemotherapy is not required if either of the following criteria is met:
- relapse within 6 months of last chemotherapy
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- blast count <30% within 10 days of starting this protocol therapy or
- Secondary AML (MDS transformation or treatment related):
- or
- AML relapsed > 2 months after transplant Subjects with prior central nervous system (CNS) involvement are eligible provided that it has been treated and Cerebrospinal fluid (CSF) is clear for at least 2 weeks prior to Visit 1.
- Subject is ≥ 18 and ≤ 70 years of age at the time of signing the informed consent form (ICF).
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study schedule and other protocol requirements.
- Karnofsky Performance Status > 50%.
- Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the PNK-007 cell infusion.
- Female of childbearing potential (FCBP) must:
- Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
- Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting PNK-007, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy. Male subjects must: a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following PNK-007 discontinuation, even if he has undergone a successful vasectomy.
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Subject has any significant medical condition, laboratory abnormality, or known psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition including the presence of laboratory abnormalities which places the subject at unacceptable risk if he or she were to participate in the study.
- A subject has any condition that confounds the ability to interpret data from the study.
- Subject has a body weight exceeding 120kg.
- Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) at screening.
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- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at screening calculated using the Modification of Diet in Renal Disease Study equation or history of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below normal in the past year.
- Subject has a bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at screening.
- Subject has had prior treatment with biologic antineoplastic agents no less than 7 days before PNK-007 infusion and at least 5 half lives. For agents that have known Adverse Events (AEs) occurring beyond 7 days after administration (ie, monoclonal antibodies), this period must be extended beyond the time during which acute AEs are known to occur. An exception to this criteria is hydroxyurea which can be given throughout the Screening/Baseline Period up to the time of the pre-conditioning treatment.
- Subject has bi-phenotypic acute leukemia.
- Subject has had a transplant < 60 days prior to Visit 1 (Screening/Baseline visit).
- Subject has had treatment for graft-versus-host disease < 30 days prior to Visit 1 (Screening/Baseline visit).
- Subject is pregnant or breastfeeding.
- Subject has new or progressive pulmonary infiltrates or pleural effusion large enough to be detected by chest x-ray or Computed tomography (CT) scan.
- Subject has active autoimmune disease other than controlled connective tissue disorder or those who are not on active therapy.
- Subject is HIV positive.
- Subject has a history of malignancy except primary, secondary, or relapsed Acute myeloid leukemia (AML), or excised and cured non-melanoma skin cancer, or cervical carcinoma in situ that was surgically ablated more than 5 years prior to PNK-007 infusion.
- Subject has a history of severe asthma and is presently on chronic medications or has a history of other symptomatic pulmonary disease.
- Untreated chronic infection or treatment of any infection with systemic antibiotics within 2 weeks prior to dosing with PNK-007.
- Subject has any other organ dysfunction (CTCAE Version 4.03 Grade 3) that will interfere with the administration of the therapy according to this protocol.
- Subject has a resting left ventricular ejection fraction (LVEF) of < 35% obtained by echocardiography or multigated acquisition scan (MUGA).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Roswell Park Cancer Center
Buffalo, New York, 14263
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Froedtert Hospital BMT Medical College of Wisconsin
Milwaukee, Wisconsin, 53226-3522
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt Univ Medical Center
Nashville, Tennessee, 37232-6307
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase 1, Multicenter, Open-Label, Dose Escalating Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (RHIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML).
This study will find the highest acceptable treatment dose of cord blood, culture expanded natural killer (NK) cells, a kind of immune cell, in patients with relapsed and/or refractory acute myeloid leukemia.
The NK cells will be given with chemotherapy and Recombinant human interleukin 2 (rhIL-2) to help the NK cells expand in the body. The safety of this treatment will be studied and researchers want to learn if NK cells will help in treating the AML.
Read the detailed description
The primary objective of the study is to assess safety and determine the maximum tolerated dose of PNK-007 in subjects with relapsed and/or refractory acute myeloid leukemia (AML). The secondary objective is to explore the potential clinical efficacy by day 42.
Treatment plan includes conditioning with cyclophosphamide and fludarabine. PNK-007 will administered IV followed by a total of six Recombinant human interleukin 2 (rhIL-2) injections to support the NK cells in the body.
Subjects will be followed for up to 24 months.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- PNK-007, Cyclophosphamide, Fludarabine, Human recombinant Interleukin-2 (rhIL-2)
- Keywords
- Acute Myeloid, Leukemia, PNK-007, Human IL-2, RHIL-2, Fludarabine, Cyclophosphamide
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PNK-007Biological
CyclophosphamideDrug
FludarabineDrug
Human recombinant Interleukin-2 (rhIL-2)Drug
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 | Experimental | Fludarabine Day -6 to -2 and Cyclophosphamide Day -5 and -4. On Day 0 PNK-007 at 4 varying dose levels followed by Human recombinant Interleukin-2 (rhIL-2) every other day, Day 0 to Day 10. Receives: Biological: PNK-007; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Human recombinant Interleukin-2 (rhIL-2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-Limiting Toxicity (DLT)
Number and severity of adverse events within 28 days of administration.
Measured: Up to approximately 28 days
Maximum Tolerated Dose (MTD)
The maximum dose safely administered for the treatment of patients with AML.
Measured: Up to approximately 28 days
Adverse Events (AEs)
Number and severity of adverse events
Measured: Up to approximately 12 months
Secondary outcomes (2)
Complete remission with incomplete platelet recovery (CRp)
CRp is defined as leukemia clearance (< 5% marrow blasts and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery.
Measured: Up to approximately 42 days
Complete remission (CR)
CR is defined as leukemia clearance (< 5% marrow blasts, no circulating peripheral blasts) in conjunction with normal values for absolute neutrophil count (> 1000/μL) and platelet count (> 100,000/μL), and independence from red cell transfusion.
Measured: Up to approximately 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2016 (estimated)
- Study start11 Jul 2016
- Primary completion7 Dec 2017
- Study completion7 Dec 2017
Why it stopped: Business Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celularity Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Solveig Ericson, MD, Study director, Celularity Incorporated
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02781467
- Sponsor's protocol ID
- CCT-PNK-007-AML-001
- Status last verified
- Dec 2017
- First submitted
- 20 May 2016
- Last updated
- 22 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-Label, Dose Escalating Safety Study of Human Cord Blood Derived, Culture Expanded Natural Killer Cell (PNK-007) Infusion With Subcutaneous Recombinant Human IL-2 (RHIL-2) in Adults With Relapsed and/or Refractory Acute Myeloid Leukemia (AML).
- ClinicalTrials.gov ID
- NCT02781467
- Acronym / sponsor ID
- CCT-PNK-007-AML-001
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- Acute Myeloid, Leukemia, PNK-007, Human IL-2, RHIL-2, Fludarabine, Cyclophosphamide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Decision
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Celularity IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 11 Jul 2016 (actual)
- Primary completion
- 7 Dec 2017 (actual)
- Study completion
- 7 Dec 2017 (actual)
- First posted
- 24 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will find the highest acceptable treatment dose of cord blood, culture expanded natural killer (NK) cells, a kind of immune cell, in patients with relapsed and/or refractory acute myeloid leukemia.
The NK cells will be given with chemotherapy and Recombinant human interleukin 2 (rhIL-2) to help the NK cells expand in the body. The safety of this treatment will be studied and researchers want to learn if NK cells will help in treating the AML.
Detailed description
The primary objective of the study is to assess safety and determine the maximum tolerated dose of PNK-007 in subjects with relapsed and/or refractory acute myeloid leukemia (AML). The secondary objective is to explore the potential clinical efficacy by day 42.
Treatment plan includes conditioning with cyclophosphamide and fludarabine. PNK-007 will administered IV followed by a total of six Recombinant human interleukin 2 (rhIL-2) injections to support the NK cells in the body.
Subjects will be followed for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 | Experimental | Biological: PNK-007, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Human recombinant Interleukin-2 (rhIL-2)Fludarabine Day -6 to -2 and Cyclophosphamide Day -5 and -4. On Day 0 PNK-007 at 4 varying dose levels followed by Human recombinant Interleukin-2 (rhIL-2) every other day, Day 0 to Day 10. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Subject has an eligible disease:
- or
- Subject is ≥ 18 and ≤ 70 years of age at the time of signing the informed consent form (ICF).
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study schedule and other protocol requirements.
Key exclusion criteria (21 listed)
- Subject has any significant medical condition, laboratory abnormality, or known psychiatric illness that would prevent the subject from participating in the study.
- Subject has any condition including the presence of laboratory abnormalities which places the subject at unacceptable risk if he or she were to participate in the study.
- A subject has any condition that confounds the ability to interpret data from the study.
- Subject has a body weight exceeding 120kg.
- Subject has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN) at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PNK-007 | Biological | Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 |
| Cyclophosphamide | Drug | Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 |
| Fludarabine | Drug | Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 |
| Human recombinant Interleukin-2 (rhIL-2) | Drug | Cyclophosphamide + Fludarabine + PNK-007 + rhIL-2 |
Primary outcome
Dose-Limiting Toxicity (DLT)
Time frame: Up to approximately 28 days
Number and severity of adverse events within 28 days of administration.
Maximum Tolerated Dose (MTD)
Time frame: Up to approximately 28 days
The maximum dose safely administered for the treatment of patients with AML.
Adverse Events (AEs)
Time frame: Up to approximately 12 months
Number and severity of adverse events
2 secondary outcomes
Complete remission with incomplete platelet recovery (CRp)
Time frame: Up to approximately 42 days
Complete remission (CR)
Time frame: Up to approximately 42 days
Results and safety
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Solveig Ericson, MD study director
Celularity Incorporated
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PNK-007, Cyclophosphamide and Fludarabine in people with Leukemia, Myeloid, Acute, run by Celularity Incorporated at 7 sites in United States.
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 18 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: stopped early, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) (time frame: Up to approximately 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jul 2020.