Acute Lymphoblastic LeukemiaPhase 1NCT00697671
Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies
A Phase 1 study testing NK Cell Infusion, Immunotherapy and Miltenyi Biotec CliniMACS device in people with Acute Lymphoblastic Leukemia and Chronic Myelogenous Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
The prognosis of pediatric patients with hematologic malignancies whose disease is primarily refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely poor. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Juvenile Myelomonocytic Leukemia
- What is being tested?
- NK Cell Infusion, Immunotherapy and Miltenyi Biotec CliniMACS device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to May 2013
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- At least two weeks since receipt of last biological therapy, chemotherapy, or radiation therapy.
- Has a suitable adult family member donor available for NK cell donation.
- No current pleural or pericardial effusion.
- HIV negative
- Adequate clinical standing as evidenced by being within multiple renal, hepatic, pulmonary, and neurological required testing parameters.
Who cannot join
- Pregnant or lactating
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
The prognosis of pediatric patients with hematologic malignancies whose disease is primarily refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely poor. When new agents or chemotherapeutic regimens are unable to induce remission in this patient population, hematopoietic stem cell transplant (HSCT) is also a poor alternative. Thus, in this very high risk group, additional attempts at remission induction with various combinations of chemotherapy alone will unlikely improve outcome and will contribute to overall toxicity. Alternative therapies are needed in these patients with chemotherapy resistant disease.
Immunotherapy with natural killer (NK) cell infusion has the potential to decrease toxicity and induce hematologic remission. NK cells can kill target cells, including leukemia cells, without prior exposure to those cells. In patients undergoing allogeneic HSCT, several studies have demonstrated the powerful effect of NK cells against leukemia. Furthermore, NK cell infusions in patients with primary refractory or multiple-relapsed leukemia have been shown to be well tolerated and void of graft-versus-host disease effects. In this high risk group, complete leukemic remission has been observed in several of these patients after NK cell infusion.
With the current technology available at St. Jude, we have developed a procedure to purify NK cells from adult donors. This protocol will assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants who have chemotherapy refractory hematologic malignancies including acute lymphoblastic leukemia, chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, or non-Hodgkin's lymphoma. In this same cohort, we will also intend to explore the efficacy of NK cells infused in those participants who have chemotherapy refractory disease.
Read the detailed description
This study will evaluate the persistence, phenotype and function of donor NK cells as well as exploring the efficacy of the infusion in research participants with chemotherapy refractory hematologic malignancies.
- Conditions
- Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome, Non-Hodgkin's Lymphoma
- Being tested
- NK Cell Infusion, Immunotherapy, Miltenyi Biotec CliniMACS device, Interleukin-2 (IL-2), Clofarabine
- Keywords
- NK cell infusion, Immunotherapy, hematologic malignancy, Miltenyi Biotec device, haploidentical donor
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Juvenile, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NK Cell InfusionOther
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued
ImmunotherapyBiological
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
Miltenyi Biotec CliniMACS deviceDevice
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
Interleukin-2 (IL-2)Drug
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
ClofarabineDrug
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
CyclophosphamideDrug
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
EtoposideDrug
All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
| Study group | Role | What they receive |
|---|---|---|
| Strata A | Other | Patients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant. Receives: Other: NK Cell Infusion; Biological: Immunotherapy; Device: Miltenyi Biotec CliniMACS device; Drug: Interleukin-2 (IL-2); Drug: Clofarabine; Drug: Cyclophosphamide; Drug: Etoposide |
| Strata B | Other | Patients with ALL, CML, JMML , MDS, or NHL with primary induction failure and persistent disease; or participants with relapsed ALL, CML, JMML, MDS, or NHL with persistent disease after re-induction Receives: Other: NK Cell Infusion; Biological: Immunotherapy; Device: Miltenyi Biotec CliniMACS device; Drug: Interleukin-2 (IL-2); Drug: Clofarabine; Drug: Cyclophosphamide; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants with chemotherapy refractory non-acute myelogenous leukemia (non-AML) hematologic malignancies
Measured: 4 months post infusion
Secondary outcomes (2)
To study the persistence, phenotype and function of donor natural killer (NK) cells after infusion in research participants with chemotherapy refractory hematologic malignancies.
Measured: 4 months infusion
To explore the efficacy of NK cell infusion in research participants with chemotherapy refractory hematologic malignancies
Measured: 4 months infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2008 (estimated)
- Study startMar 2007
- Primary completionFeb 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Assisi Foundation
- Responsible party
- Sponsor
- Investigators
- Wing Leung, MD, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00697671
- Sponsor's protocol ID
- NKHEM
- Status last verified
- Jul 2013
- First submitted
- 14 Apr 2008
- Last updated
- 16 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00697671
- Acronym / sponsor ID
- NKHEM
- Conditions
- Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome, Non-Hodgkin's Lymphoma
- Keywords
- NK cell infusion, Immunotherapy, hematologic malignancy, Miltenyi Biotec device, haploidentical donor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Assisi Foundation
- Study start
- Mar 2007
- Primary completion
- Feb 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 Jun 2008 (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.
The prognosis of pediatric patients with hematologic malignancies whose disease is primarily refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely poor. When new agents or chemotherapeutic regimens are unable to induce remission in this patient population, hematopoietic stem cell transplant (HSCT) is also a poor alternative. Thus, in this very high risk group, additional attempts at remission induction with various combinations of chemotherapy alone will unlikely improve outcome and will contribute to overall toxicity. Alternative therapies are needed in these patients with chemotherapy resistant disease.
Immunotherapy with natural killer (NK) cell infusion has the potential to decrease toxicity and induce hematologic remission. NK cells can kill target cells, including leukemia cells, without prior exposure to those cells. In patients undergoing allogeneic HSCT, several studies have demonstrated the powerful effect of NK cells against leukemia. Furthermore, NK cell infusions in patients with primary refractory or multiple-relapsed leukemia have been shown to be well tolerated and void of graft-versus-host disease effects. In this high risk group, complete leukemic remission has been observed in several of these patients after NK cell infusion.
With the current technology available at St. Jude, we have developed a procedure to purify NK cells from adult donors. This protocol will assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants who have chemotherapy refractory hematologic malignancies including acute lymphoblastic leukemia, chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, or non-Hodgkin's lymphoma. In this same cohort, we will also intend to explore the efficacy of NK cells infused in those participants who have chemotherapy refractory disease.
Detailed description
This study will evaluate the persistence, phenotype and function of donor NK cells as well as exploring the efficacy of the infusion in research participants with chemotherapy refractory hematologic malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Strata A | Other | Other: NK Cell Infusion, Biological: Immunotherapy, Device: Miltenyi Biotec CliniMACS device, Drug: Interleukin-2 (IL-2), Drug: Clofarabine, Drug: Cyclophosphamide, Drug: EtoposidePatients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant. |
| Strata B | Other | Other: NK Cell Infusion, Biological: Immunotherapy, Device: Miltenyi Biotec CliniMACS device, Drug: Interleukin-2 (IL-2), Drug: Clofarabine, Drug: Cyclophosphamide, Drug: EtoposidePatients with ALL, CML, JMML , MDS, or NHL with primary induction failure and persistent disease; or participants with relapsed ALL, CML, JMML, MDS, or NHL with persistent disease after re-induction |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- At least two weeks since receipt of last biological therapy, chemotherapy, or radiation therapy.
- Has a suitable adult family member donor available for NK cell donation.
- No current pleural or pericardial effusion.
- HIV negative
- Adequate clinical standing as evidenced by being within multiple renal, hepatic, pulmonary, and neurological required testing parameters.
Key exclusion criteria (1 listed)
- Pregnant or lactating
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 |
|---|---|---|
| NK Cell InfusionAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued | Other | Strata A, Strata B |
| ImmunotherapyAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Biological | Strata A, Strata B |
| Miltenyi Biotec CliniMACS deviceAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Device | Strata A, Strata B |
| Interleukin-2 (IL-2)All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Drug | Strata A, Strata B |
| ClofarabineAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Drug | Strata A, Strata B |
| CyclophosphamideAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Drug | Strata A, Strata B |
| EtoposideAll participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued. | Drug | Strata A, Strata B |
Primary outcome
To assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants with chemotherapy refractory non-acute myelogenous leukemia (non-AML) hematologic malignancies
Time frame: 4 months post infusion
2 secondary outcomes
To study the persistence, phenotype and function of donor natural killer (NK) cells after infusion in research participants with chemotherapy refractory hematologic malignancies.
Time frame: 4 months infusion
To explore the efficacy of NK cell infusion in research participants with chemotherapy refractory hematologic malignancies
Time frame: 4 months infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2013.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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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.
Wing Leung, MD, PhD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NK Cell Infusion, Immunotherapy and Miltenyi Biotec CliniMACS device in people with Acute Lymphoblastic Leukemia and Chronic Myelogenous Leukemia, run by St. Jude Children's Research Hospital at 1 site 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 5 inclusion and 1 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: finished, as of the sponsor's last update on 16 Jul 2013. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants with chemotherapy refractory non-acute myelogenous leukemia (non-AML) hematologic malignancies (time frame: 4 months post infusion). 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 16 Jul 2013.