Hematologic MalignancyPhase 1/2NCT05250362
Ex Vivo Expanded NK Cells Infusion Decrease Relapse Post Hematopoietic Stem Cell Transplantation
A Phase 1/2 study testing Allogeneic Hematopoietic Stem Cell Transplantation in people with Hematologic Malignancy, run by Sichuan University at 1 site in China.
Trial summary
This phase I/II study the side effects and efficacy of natural killer cells after donor stem cell transplant and how they treat patients with myeloid malignancies or lymphoproliferative disorders. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Hematologic Malignancy
- What is being tested?
- Allogeneic Hematopoietic Stem Cell Transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2022to 31 Dec 2025
- Phase
- Phase 1/2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient with no matched related donor who has a related haploidentical donor identified (=< 7/8 allele match at the A, B, C, DR loci) who is willing to undergo a bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's admission for transplant; the donor must be 16 years of age or older and weigh at least 50kg.
- Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g., DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (> 3 abnormalities); (vi) treatment-related AML, or b. second or more significant remission; patients beyond the second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
- Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy or b. patients with treatment-related MDS
- Chronic myeloid leukemia (CML): a. failed to achieve cytogenetic remission or have a cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b. accelerated phase or blast phase at any time
- Lymphoma: a. refractory to or released from 1st line therapy, salvaged by 2nd line therapy, or b. high-risk lymphoma with CR to 1st line therapy.
- Performance score of at least 70% by Karnofsky or 0 to 1 by Eastern Cooperative Oncology Group (ECOG) (age >= 12 years), or Lansky Play-performance scale of at least 70% or greater (age < 12 years)
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- Serum creatinine clearance equal to or more than 50 ml/min (calculated with Cockcroft-Gault formula)
- Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or less than 200 IU/ml for adults
- Conjugated (direct) bilirubin less than 2 x upper limit of normal
- Left ventricular ejection fraction equal to or greater than 40%
- Diffusing capacity of the lung for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin; for children =< 7 years of age who are unable to perform pulmonary function tests (PFT), oxygen saturation >= 92% on room air by pulse oximetry
- 11. Patient or patient's legal representative, parent(s), or guardian should provide written informed consent; the permission of a minor if participant's age is at least seven and less than eighteen years
Who cannot join
- Human immunodeficiency virus (HIV) positive; active hepatitis B or C
- Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion Liver cirrhosis
- Central nervous system (CNS) involvement within three months
- Positive pregnancy test in a woman with childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
- Inability to comply with medical therapy or follow-up
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
West China Hospital of Sichuan University
Chengdu, Sichuan, 610044
Jie Ji, MD, 86-28-85422370, jieji@scu.edu.cn
About this study
Official title: Non-feeder Cell ex Vivo Expanded Allogeneic NK Cells Infusion Decrease Relapse Post Hematopoietic Stem Cell Transplantation.
This phase I/II study the side effects and efficacy of natural killer cells after donor stem cell transplant and how they treat patients with myeloid malignancies or lymphoproliferative disorders. Investigators expanded NK cells ex vivo with a non-feeder cell regimen to avoid the risk of infusion of feeder cells with expanded NK cells. Investigators infuse NK cells after myeloablative conditioning therapy. These cells may help decrease relapse of malignant disease, severe graft versus host disease, reactivation of certain viruses, and, therefore, prolong the survival of participants.
- Conditions
- Hematologic Malignancy
- Being tested
- Allogeneic Hematopoietic Stem Cell Transplantation
- Keywords
- NK cell, stem cell transplant, relapse
- Medical subject headings
- Hematologic Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
MYELOABLATIVE CONDITIONING REGIMEN: Patients with myeloid malignancies receive busulfan on days -7 to -4, fludarabine IV over 1 hour on days -7 to -3, cytarabine IV over 4 hours on days -7 to -3. Patients with lymphoproliferative disorders receive busulfan on day -7 to -4, cladribine IV over 1 hour on days -7 to -3, gemcitabine IV over 4 hours on days -7 and -3.
TRANSPLANT: Patients undergo PBSC transplant on day 0.
POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, cyclosporin IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO BID beginning on day 5 for 30 days.
NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated doses (MTD) of natural killer (NK) cells
Primary Outcome Measures
Measured: Up to day 70 post-transplant
Secondary outcomes (4)
100-day treatment related mortality
Will be defined as death due to any cause without disease recurrence within 100 days post stem cell transplant (SCT). The method of Thall and Sung will be used, based on an historical rate of 35%.
Measured: Up to 100 days post-transplant
Overall survival
Will be estimated using the Kaplan-Meier method, and distributions will be compared using log-rank tests.
Measured: Up to 2 years post-transplant
Relapse-free survival
Will be estimated using the Kaplan-Meier method, and distributions will be compared using log-rank tests.
Measured: Up to 2 years post-transplant
Time to engraftment
Will be estimated using the Kaplan-Meier method, and distributions will be compared using log-rank tests.
Measured: Up to 2 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2022
- Study start1 Mar 2022
- Primary completion28 Feb 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- intervention: Expanded NK cells
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sichuan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jie Ji, Sichuan University
- Investigators
- Jie Ji, MD, Principal investigator, West China Hospital, Sichuan Uiversity
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05250362
- Sponsor's protocol ID
- HXNKI1.0
- Status last verified
- Mar 2022
- First submitted
- 11 Feb 2022
- Last updated
- 15 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-feeder Cell ex Vivo Expanded Allogeneic NK Cells Infusion Decrease Relapse Post Hematopoietic Stem Cell Transplantation.
- ClinicalTrials.gov ID
- NCT05250362
- Acronym / sponsor ID
- HXNKI1.0
- Conditions
- Hematologic Malignancy
- Keywords
- NK cell, stem cell transplant, relapse
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Sichuan UniversityUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 28 Feb 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 22 Feb 2022 (actual)
- 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 phase I/II study the side effects and efficacy of natural killer cells after donor stem cell transplant and how they treat patients with myeloid malignancies or lymphoproliferative disorders. Investigators expanded NK cells ex vivo with a non-feeder cell regimen to avoid the risk of infusion of feeder cells with expanded NK cells. Investigators infuse NK cells after myeloablative conditioning therapy. These cells may help decrease relapse of malignant disease, severe graft versus host disease, reactivation of certain viruses, and, therefore, prolong the survival of participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- intervention: Expanded NK cells
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Patient with no matched related donor who has a related haploidentical donor identified (=< 7/8 allele match at the A, B, C, DR loci) who is willing to undergo a bone marrow harvest and an NK cell collection approximately 2 weeks of the recipient's admission for transplant; the donor must be 16 years of age or older and weigh at least 50kg.
- Patients with one of the following diseases: acute myeloid leukemia (AML): a. first complete remission with high-risk features defined as (i) greater than 1 cycle of induction therapy required to achieve remission; (ii) preceding myelodysplastic syndrome (MDS); (iii) presence of FLT3 mutations or internal tandem duplication or other mutations associated with poor-risk AML (e.g., DNMT3A, TET2); (iv) French-American-British Classification (FAB) M6 or M7 classification; (v) adverse cytogenetics: -5, deletion (del) 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype (> 3 abnormalities); (vi) treatment-related AML, or b. second or more significant remission; patients beyond the second remission have to be in complete remission (CR) at transplant to be eligible, or c. primary induction failure with partial response to therapy who achieve adequate cytoreduction
- Patients with myelodysplastic syndromes (MDS): a. de novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores; patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy or b. patients with treatment-related MDS
- Chronic myeloid leukemia (CML): a. failed to achieve cytogenetic remission or have a cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or b. accelerated phase or blast phase at any time
- Lymphoma: a. refractory to or released from 1st line therapy, salvaged by 2nd line therapy, or b. high-risk lymphoma with CR to 1st line therapy.
Key exclusion criteria (5 listed)
- Human immunodeficiency virus (HIV) positive; active hepatitis B or C
- Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion Liver cirrhosis
- Central nervous system (CNS) involvement within three months
- Positive pregnancy test in a woman with childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
- Inability to comply with medical therapy or follow-up
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 |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell TransplantationMYELOABLATIVE CONDITIONING REGIMEN: Patients with myeloid malignancies receive busulfan on days -7 to -4, fludarabine IV over 1 hour on days -7 to -3, cytarabine IV over 4 hours on days -7 to -3. Patients with lymphoproliferative disorders receive busulfan on day -7 to -4, cladribine IV over 1 hour on days -7 to -3, gemcitabine IV over 4 hours on days -7 and -3. TRANSPLANT: Patients undergo PBSC transplant on day 0. POST-TRANSPLANT CYCLOPHOSPHAMIDE AND GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, cyclosporin IV beginning on day 5 for 2 weeks and then PO for approximately 4 months, and mycophenolate mofetil PO BID beginning on day 5 for 30 days. NK CELLS: Patients receive NK cells IV over 30 minutes on days 7 and 28. | Procedure or surgery | Treatment |
Primary outcome
Maximum tolerated doses (MTD) of natural killer (NK) cells
Time frame: Up to day 70 post-transplant
Primary Outcome Measures
4 secondary outcomes
100-day treatment related mortality
Time frame: Up to 100 days post-transplant
Overall survival
Time frame: Up to 2 years post-transplant
Relapse-free survival
Time frame: Up to 2 years post-transplant
Time to engraftment
Time frame: Up to 2 years post-transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
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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.
Jie Ji, MD principal investigator
West China Hospital, Sichuan Uiversity
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic Hematopoietic Stem Cell Transplantation in people with Hematologic Malignancy, run by Sichuan University at 1 site in China.
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 12 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jie Ji, MD (86-28-85422373, jieji@scu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated doses (MTD) of natural killer (NK) cells (time frame: Up to day 70 post-transplant). 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 15 Mar 2022.