LeukemiaPhase 2NCT01807611
Haploidentical Donor Hematopoietic Progenitor Cell and NK Cell Transplantation for Hematologic Malignancy
A Phase 2 study testing Total Lymphoid Irradiation, Fludarabine and Cyclophosphamide in people with Leukemia and Lymphoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional… Read more about this study
- Who is it for?
- Ages Up to 21 years
- What is being tested?
- Total Lymphoid Irradiation, Fludarabine and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2013to 27 Sep 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age less than or equal to 21 years.
- Does not have a suitable MSD or volunteer MUD available in the necessary time for stem cell donation.
- Has a suitable single haplotype matched (≥ 3 of 6) and family member donor.
- High risk hematologic malignancy.
- If prior CNS leukemia, it must be treated and in CNS CR
- Does not have any other active malignancy other than the one for which this HCT is indicated.
Show all 14Show fewer
- No prior allogeneic HCT, and no autologous HCT within the previous 12 months.
- Patient must fulfill pre-transplant evaluation
- At least single haplotype matched (≥ 3 of 6) family member
- At least 18 years of age.
- HIV negative.
- Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
- Not breast feeding.
- Regarding eligibility, is identified as either: (1) Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR (2) Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.
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: Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells.
The investigators anticipate enrollment of 75 donors and 75 recipients.
Read more
PRIMARY OBJECTIVE:
- To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy.
SECONDARY OBJECTIVES:
- Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
- Estimate incidence and severity of acute and chronic (GVHD).
- Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
Read the detailed description
Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK).
The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts.
Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.
- Being tested
- Total Lymphoid Irradiation, Fludarabine, Cyclophosphamide, Thiotepa, Melphalan
- Keywords
- Haploidentical donor transplantation, NK cell
- Medical subject headings
- Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Lymphoid IrradiationRadiation
Also called TLI
Participants receive total lymphoid irradiation over four doses.
FludarabineDrug
Also called Fludara
Given IV.
CyclophosphamideDrug
Also called Cytoxan
Given IV.
ThiotepaDrug
Also called Thioplex(R) by Immunex, TESPA, TSPA
Given IV.
MelphalanDrug
Also called L-phenylalanine mustard, Phenylalanine Mustard, L-PAM, L-sarcolysin
Given IV.
HPC,A InfusionBiological
Participants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted).
TC-NK InfusionBiological
Participants receive infusions of TC-NK.
G-CSFBiological
Also called Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen(R)
Participants receive G-CSF subcutaneously or intravenously.
Donors receive G-CSF subcutaneously during cell mobilization.
MesnaDrug
Also called Mesnex
Mesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide.
CliniMACSDevice
Also called Cell Selection System
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Also called MMF, CellCept®
Given intravenously or orally.
| Study group | Role | What they receive |
|---|---|---|
| Transplant Recipients | Experimental | Participants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna.
Cells for infusion are prepared using the CliniMACS System. Receives: Radiation: Total Lymphoid Irradiation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Thiotepa; Drug: Melphalan; Biological: HPC,A Infusion; Biological: TC-NK Infusion; Biological: G-CSF; Drug: Mesna; Device: CliniMACS; Drug: Mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Transplant Recipients With Successful Engraftment
Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.
Measured: 42 days post engraftment
Secondary outcomes (7)
Number of Transplant Recipients With Malignant Relapse
Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Measured: One-year post-transplantation
Event-free Survival
The one-year event free survival is defined by the patient who has neither experienced relapse nor death within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year event free survival patients and the total number of patients.
Measured: One year post-transplantation
Overall Survival
The one-year survival is defined by the patient who has not died within one year after post transplantation. And the rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Measured: one year post-transplantation
Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)
Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The estimate will be the number of recipients who experienced GVHD divided by the total number of patients considered in this group.
Measured: 100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .
Number of Transplant Recipients With Transplant-related Mortality (TRM)
Estimate the proportion of patients died within 100 days after the transplantation who has not experienced a relapse. The estimate will be the number of TRM divides the total number of patients considered in this group.
Measured: In the first 100 days after transplantation
Severity of Acute Graft Versus Host Disease (aGVHD)
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 100 days post transplant. Acute GvHD is graded from 1-4 with 4 being the worst outcome.
Measured: 100 days post-transplant for acute GVHD.
Severity of Chronic Graft Versus Host Disease (cGVHD)
Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The severity of acute GvHD and chronic GvHD will be described. The analysis for this objective will be performed when the last evaluable participant has been followed for 1 year post-transplant. Chronic GvHD is graded as "mild", "moderate" or "severe" with "severe" being the worst outcome.
Measured: 1 year post-transplant for chronic GVHD .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2013 (estimated)
- Study start16 May 2013
- Primary completion27 Aug 2021
- Study completion27 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 82 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
- Brandon M. Triplett, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01807611
- Sponsor's protocol ID
- HAPNK1
- Other IDs
- NCI-2013-00609
- Status last verified
- Aug 2022
- First submitted
- 5 Mar 2013
- Last updated
- 31 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Naik S, Li Y, Talleur AC, Selukar S, Ashcraft E, Cheng C, Madden RM, Mamcarz E, Qudeimat A, Sharma A, Srinivasan A, Suliman AY, Epperly R, Obeng EA, Velasquez MP, Langfitt D, Schell S, Metais JY, Arnold PY, Hijano DR, Maron G, Merchant TE, Akel S, Leung W, Gottschalk S, Triplett BM. Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial. J Hematol Oncol. 2024 Jun 27;17(1):50. doi: 10.1186/s13045-024-01567-0.
PubMed 38937803
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Donor Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation With a TLI Based Conditioning Regimen in Patients With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01807611
- Acronym / sponsor ID
- HAPNK1
- Keywords
- Haploidentical donor transplantation, NK cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Assisi Foundation
- Study start
- 16 May 2013 (actual)
- Primary completion
- 27 Aug 2021 (actual)
- Study completion
- 27 Sep 2021 (actual)
- First posted
- 8 Mar 2013 (estimated)
- Results
- Posted 31 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA) matched related/sibling donor (MSD) or matched unrelated donor (MUD) identified, will receive a haploidentical donor HCT with additional natural killer (NK) cells.
The investigators anticipate enrollment of 75 donors and 75 recipients.
PRIMARY OBJECTIVE:
- To estimate the rate of successful engraftment at day +42 post-transplant in patients who receive haploidentical donor stem cell plus NK cell transplantation with TLI based conditioning regimen for high risk hematologic malignancy.
SECONDARY OBJECTIVES:
- Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
- Estimate incidence and severity of acute and chronic (GVHD).
- Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
Detailed description
Donors will undergo G-CSF mobilization of peripheral blood stem cells (PBSC) prior to undergoing two apheresis collections of hematopoietic progenitor cells (HPC,A) and one apheresis collection of therapeutic cell product of purified natural killer cells (TC-NK).
The HPC products will be T-cell depleted (TCD) using the investigational CliniMACS device. CD34+ enrichment and CD45RA depletion will be utilized on sequential HPC grafts.
Participants will undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, granulocyte colony stimulating factor (G-CSF), thiotepa, and melphalan. This is followed by infusions of donor cells that have been prepared using the CliniMACS system: HPC,A (CD34+ selected), HPC,A (CD45RA depleted), and TC-NK.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant Recipients | Experimental | Radiation: Total Lymphoid Irradiation, Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Thiotepa, Drug: Melphalan, Biological: HPC,A Infusion, Biological: TC-NK Infusion, Biological: G-CSF, Drug: Mesna, Device: CliniMACS, Drug: Mycophenolate mofetilParticipants undergo a preparative regimen of total lymphoid irradiation, fludarabine, cyclophosphamide, fludarabine, thiotepa, melphalan, and mycophenolate mofetil, followed by HPC,A infusion and TC-NK infusion. They also receive G-CSF and mesna. Cells for infusion are prepared using the CliniMACS System. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Age less than or equal to 21 years.
- Does not have a suitable MSD or volunteer MUD available in the necessary time for stem cell donation.
- Has a suitable single haplotype matched (≥ 3 of 6) and family member donor.
- High risk hematologic malignancy.
- If prior CNS leukemia, it must be treated and in CNS CR
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 |
|---|---|---|
| Total Lymphoid IrradiationAlso: TLIParticipants receive total lymphoid irradiation over four doses. | Radiation | Transplant Recipients |
| FludarabineAlso: FludaraGiven IV. | Drug | Transplant Recipients |
| CyclophosphamideAlso: CytoxanGiven IV. | Drug | Transplant Recipients |
| ThiotepaAlso: Thioplex(R) by Immunex, TESPA, TSPAGiven IV. | Drug | Transplant Recipients |
| MelphalanAlso: L-phenylalanine mustard, Phenylalanine Mustard, L-PAM, L-sarcolysinGiven IV. | Drug | Transplant Recipients |
| HPC,A InfusionParticipants received infusions of HPC,A (CD34+ selected) and HPC,A (CD45RA depleted). | Biological | Transplant Recipients |
| TC-NK InfusionParticipants receive infusions of TC-NK. | Biological | Transplant Recipients |
| G-CSFAlso: Granulocyte Colony-Stimulating Factor, Filgrastim, Neupogen(R)Participants receive G-CSF subcutaneously or intravenously. Donors receive G-CSF subcutaneously during cell mobilization. | Biological | Transplant Recipients |
| MesnaAlso: MesnexMesna is generally dosed at approximately 25% of the cyclophosphamide dose. It is generally given intravenously prior to and again at 3, 6 and 9 hours following each dose of cyclophosphamide. | Drug | Transplant Recipients |
| CliniMACSAlso: Cell Selection SystemThe mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells. | Device | Transplant Recipients |
| Mycophenolate mofetilAlso: MMF, CellCept®Given intravenously or orally. | Drug | Transplant Recipients |
Primary outcome
Number of Transplant Recipients With Successful Engraftment
Time frame: 42 days post engraftment
Neutrophil engraftment will be determined using the parameters put forth by the Center for International Blood and Marrow Registry. Assessments will be made upon review of daily complete blood count and serial chimerism studies. Successful engraftment for the purposes of this objective will be patients who do not experience graft failure.
7 secondary outcomes
Number of Transplant Recipients With Malignant Relapse
Time frame: One-year post-transplantation
Event-free Survival
Time frame: One year post-transplantation
Overall Survival
Time frame: one year post-transplantation
Number of Transplant Recipients With Acute and/or Chronic Graft Versus Host Disease (GVHD)
Time frame: 100 days post-transplant for acute GVHD; one year post-transplant for chronic GVHD .
Number of Transplant Recipients With Transplant-related Mortality (TRM)
Time frame: In the first 100 days after transplantation
Severity of Acute Graft Versus Host Disease (aGVHD)
Time frame: 100 days post-transplant for acute GVHD.
Severity of Chronic Graft Versus Host Disease (cGVHD)
Time frame: 1 year post-transplant for chronic GVHD .
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38937803Naik S, Li Y, Talleur AC, Selukar S, Ashcraft E, Cheng C, Madden RM, Mamcarz E, Qudeimat A, Sharma A, Srinivasan A, Suliman AY, Epperly R, Obeng EA, Velasquez MP, Langfitt D, Schell S, Metais JY, Arnold PY, Hijano DR, Maron G, Merchant TE, Akel S, Leung W, Gottschalk S, Triplett BM. Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial. J Hematol Oncol. 2024 Jun 27;17(1):50. doi: 10.1186/s13045-024-01567-0.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink 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.
Brandon M. Triplett, 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 2 study testing Total Lymphoid Irradiation, Fludarabine and Cyclophosphamide in people with Leukemia and Lymphoma, 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 14 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 31 Oct 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 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 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?
Yes. Results are posted in the registry (first posted 31 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Transplant Recipients With Successful Engraftment (time frame: 42 days post engraftment). 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 NCT01807611, which also lists 1 linked publication.
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 31 Oct 2022.