Leukemia, Myeloid, AcutePhase 1NCT00640796
Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors
A Phase 1 study testing Haploidentical donor derived natural killer cell infusion, Chemotherapy and CliniMACS in people with Leukemia, Myeloid, Acute and Leukemia, Lymphocytic, Acute, T-Cell, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Modern frontline therapy for patients with hematologic malignancies is based on intensive administration of multiple drugs. In patients with relapsed disease, response to the same drugs is generally poor, and dosages cannot be further increased without unacceptable toxicities. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute, T-Cell, Juvenile Myelomonocytic Leukemia Lymphoblastic
- What is being tested?
- Haploidentical donor derived natural killer cell infusion, Chemotherapy and CliniMACS
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Apr 2014
- 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
- Less than or equal to 18 years of age (may be greater than 18 years of age if currently a St. Jude patient).
- Patients with relapsed or refractory AML, T-ALL/T-LL, mixed lineage leukemia, CML, JMML, MDS, ESFT or RMS who are not eligible for SCT and have persistent disease after remission induction(s) therapy as evidenced by bone marrow morphology, cytogenetics, flow cytometry, molecular pathology, and/or restaging scans.
- At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
- Shortening fraction greater than or equal to 25%.
- Creatinine clearance or glomerular filtration rate greater than or equal to 50 cc/min/1.73 m^2.
- Pulse oximetry greater than or equal to 92% on room air.
Show all 24Show fewer
- Direct bilirubin less than or equal to 3.0 mg/dL.
- Karnofsky or Lansky performance score of greater than or equal to 50.
- No known allergy to murine products or HAMA testing results within normal limits.
- Does not have a current pleural or pericardial effusion.
- Has a suitable adult family member donor available for NK cell donation.
- Is not receiving more than the equivalent of prednisone 10 mg daily.
- Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
- Not breast feeding.
- Eligibility criteria prior to initiation of protocol therapy (preparative regimen)
- Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.
- Aspartate transaminase (AST) is no more than 2 times the upper limit of normal.
- Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the principal investigator
- Eligibility criteria (NK cell DONOR):
- Family member with a greater than or equal to 3 of 6 HLA match to recipient.
- At least 18 years of age.
- HIV negative.
- Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
- Not breast feeding.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors
Modern frontline therapy for patients with hematologic malignancies is based on intensive administration of multiple drugs. In patients with relapsed disease, response to the same drugs is generally poor, and dosages cannot be further increased without unacceptable toxicities. For most patients, particularly those who relapse while still receiving frontline therapy, the only therapeutic option is hematopoietic stem cell transplantation (SCT). For those who relapse after transplant, or who are not eligible for transplant because of persistent disease, there is no proven curative therapy.
There is mounting evidence that NK cells have powerful anti-leukemia activity. In patients undergoing allogeneic SCT, several studies have demonstrated NK-mediated anti-leukemic activity. 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 (GVHD) effects. Myeloid leukemias are particularly sensitive to NK cells cytotoxicity, while B-lineage acute lymphoblastic leukemia (ALL) cells are often NK-resistant. We have developed a novel method to expand NK cells and enhance their cytotoxicity. Expanded and activated donor NK cells have shown powerful anti-leukemic activity against acute myeloid leukemia (AML) cells and T-lineage ALL cells in vitro and in animal models of leukemia.
The present study represents the translation of these laboratory findings into clinical application.We propose to determine the safety of infusing expanded NK cells in pediatric patients who have chemotherapy refractory or relapse hematologic malignancies including AML, T-lineage ALL, T-cell lymphoblastic lymphoma (T-LL), chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML),myelodysplastic syndrome (MDS), Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS). The NK cells used for this study will be obtained from the patient's family member who will be a partial match to the patient's immune type (HLA type).
Read the detailed description
Secondary objectives include the evaluation of the in vivo lifespan and phenotype of the expanded NK cells and explore the efficacy of these donor NK cells in study participants with relapsed or refractory hematologic malignancies or sarcomas.
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute, T-Cell, Juvenile Myelomonocytic Leukemia Lymphoblastic, T-cell Lymphoblastic Lymphoma, Myelodysplastic Syndrome
- Being tested
- Haploidentical donor derived natural killer cell infusion, Chemotherapy, CliniMACS
- Keywords
- Hematologic malignancies, non-B lineage, NK cell expansion, CliniMACS device, Immunotherapy
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical donor derived natural killer cell infusionProcedure or surgery
Therapeutic cell infusion
ChemotherapyDrug
Also called cyclophosphamide: cytoxan, fludarabine: Fludara(R), interleukin-2: IL-2, aldesleukin, Proleukin(R), mesna: Mesnex(R)
Cyclophosphamide, Fludarabine, Interleukin-2, Mesna
CliniMACSDevice
Cell selection system based on magnetic-activated cell sorting
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants undergo haploidentical donor derived natural killer cell infusion (cells obtained from donors and selected using CliniMACS cell selection system) and chemotherapy (cyclophosphamide, fludarabine, interleukin-2, mesna). Receives: Procedure: Haploidentical donor derived natural killer cell infusion; Drug: Chemotherapy; Device: CliniMACS |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of expanded NK cells in research participants with relapsed or refractory hematologic malignancies and sarcomas.
Measured: 4 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study startSep 2008
- Primary completionApr 2014
- Study completionApr 2014
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Assisi Foundation
- Responsible party
- Sponsor
- Investigators
- David Shook, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640796
- Sponsor's protocol ID
- NKEXP
- Other IDs
- R01CA113482
- Status last verified
- Apr 2014
- First submitted
- 14 Mar 2008
- Last updated
- 24 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors
- ClinicalTrials.gov ID
- NCT00640796
- Acronym / sponsor ID
- NKEXP
- Conditions
- Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute, T-Cell, Juvenile Myelomonocytic Leukemia Lymphoblastic, T-cell Lymphoblastic Lymphoma, Myelodysplastic Syndrome
- Keywords
- Hematologic malignancies, non-B lineage, NK cell expansion, CliniMACS device, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Assisi Foundation
- Study start
- Sep 2008
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 21 Mar 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.
Modern frontline therapy for patients with hematologic malignancies is based on intensive administration of multiple drugs. In patients with relapsed disease, response to the same drugs is generally poor, and dosages cannot be further increased without unacceptable toxicities. For most patients, particularly those who relapse while still receiving frontline therapy, the only therapeutic option is hematopoietic stem cell transplantation (SCT). For those who relapse after transplant, or who are not eligible for transplant because of persistent disease, there is no proven curative therapy.
There is mounting evidence that NK cells have powerful anti-leukemia activity. In patients undergoing allogeneic SCT, several studies have demonstrated NK-mediated anti-leukemic activity. 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 (GVHD) effects. Myeloid leukemias are particularly sensitive to NK cells cytotoxicity, while B-lineage acute lymphoblastic leukemia (ALL) cells are often NK-resistant. We have developed a novel method to expand NK cells and enhance their cytotoxicity. Expanded and activated donor NK cells have shown powerful anti-leukemic activity against acute myeloid leukemia (AML) cells and T-lineage ALL cells in vitro and in animal models of leukemia.
The present study represents the translation of these laboratory findings into clinical application.We propose to determine the safety of infusing expanded NK cells in pediatric patients who have chemotherapy refractory or relapse hematologic malignancies including AML, T-lineage ALL, T-cell lymphoblastic lymphoma (T-LL), chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML),myelodysplastic syndrome (MDS), Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS). The NK cells used for this study will be obtained from the patient's family member who will be a partial match to the patient's immune type (HLA type).
Detailed description
Secondary objectives include the evaluation of the in vivo lifespan and phenotype of the expanded NK cells and explore the efficacy of these donor NK cells in study participants with relapsed or refractory hematologic malignancies or sarcomas.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Procedure: Haploidentical donor derived natural killer cell infusion, Drug: Chemotherapy, Device: CliniMACSParticipants undergo haploidentical donor derived natural killer cell infusion (cells obtained from donors and selected using CliniMACS cell selection system) and chemotherapy (cyclophosphamide, fludarabine, interleukin-2, mesna). |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Less than or equal to 18 years of age (may be greater than 18 years of age if currently a St. Jude patient).
- Patients with relapsed or refractory AML, T-ALL/T-LL, mixed lineage leukemia, CML, JMML, MDS, ESFT or RMS who are not eligible for SCT and have persistent disease after remission induction(s) therapy as evidenced by bone marrow morphology, cytogenetics, flow cytometry, molecular pathology, and/or restaging scans.
- At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
- Shortening fraction greater than or equal to 25%.
- Creatinine clearance or glomerular filtration rate greater than or equal to 50 cc/min/1.73 m^2.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Haploidentical donor derived natural killer cell infusionTherapeutic cell infusion | Procedure or surgery | Treatment |
| ChemotherapyAlso: cyclophosphamide: cytoxan, fludarabine: Fludara(R), interleukin-2: IL-2, aldesleukin, Proleukin(R), mesna: Mesnex(R)Cyclophosphamide, Fludarabine, Interleukin-2, Mesna | Drug | Treatment |
| CliniMACSCell selection system based on magnetic-activated cell sorting | Device | Treatment |
Primary outcome
To determine the maximum tolerated dose of expanded NK cells in research participants with relapsed or refractory hematologic malignancies and sarcomas.
Time frame: 4 Years
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 24 Apr 2014.
- 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.
David Shook, MD 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 Haploidentical donor derived natural killer cell infusion, Chemotherapy and CliniMACS in people with Leukemia, Myeloid, Acute and Leukemia, Lymphocytic, Acute, T-Cell, 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 24 inclusion and 0 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 24 Apr 2014. 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 determine the maximum tolerated dose of expanded NK cells in research participants with relapsed or refractory hematologic malignancies and sarcomas. (time frame: 4 Years). 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 24 Apr 2014.