Acute Lymphoblastic LeukemiaPhase 2NCT02646839
KIR Favorable Mismatched Haplo Transplant and KIR Polymorphism in ALL/AML/MDS Allo-HCT Children
A Phase 2 study testing CliniMacs TCR alpha-beta-Biotin system in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Michael Pulsipher at 11 sites in United States.
Trial summary
This is a phase II, open-label, non-randomized, prospective study of haploidentical transplantation using KIR-favorable donors for children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- CliniMacs TCR alpha-beta-Biotin system
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 11 sitesUnited States
- Study dates
- Oct 2015to Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- 2.3.1 Inclusion Criteria for the Biology (KIR2DL1 Polymorphisms/ALL MRD), Comparative Outcomes, and Cost Effectiveness Trial
- Any patient with ALL, AML, or MDS who is deemed eligible for and undergoes HCT at participating centers who provides consent for the KIR2DL1 polymorphisms, comparative outcomes and cost-effectiveness portion of the trial.
- Any ALL patient undergoing allogeneic HCT at participating centers is eligible for the ALL deep sequence MRD portion of the trial.
- Patients ineligible for the KIR-favorable haploidentical phase II trial who require T-cell depletion may be treated using TCR αβ+CD3+/CD19+ cell depletion. These patients will be followed descriptively on this portion of the trial. Preparative regimen will be at the discretion of the transplant center, but the options associated with this protocol are recommended.
- 2.3.2 Inclusion Criteria for the KIR-favorable Haploidentical Phase II trial:
- Age < 22 years
Show all 25Show fewer
- Disease and disease status:
- ALL high-risk in first remission (<5% blasts by morphology pre-transplant) meeting criteria for transplant. Example CR1 indications: induction failure (>5% blasts by morphology on post-induction BM), minimal residual disease greater than or equal to 1% marrow blasts by morphology after induction, minimal residual disease by flow cytometry >0.01% after consolidation, hypodiploidy (<44 chromosomes), persistent or recurrent cytogenetic or molecular evidence of disease during therapy requiring additional therapy after induction to achieve remission (e.g. persistent molecular BCR-ABL positivity).
- ALL in second remission: B-cell; early (less than or equal to 36 months from initiation of therapy) BM relapse, late BM relapse with MRD >0.1% by flow cytometry after first induction therapy; T-cell or Ph+ with BM relapse at any time; very early (less than 18 months from initiation of therapy) isolated extramedullary relapse (T or B-cell)
- Myelodysplastic syndrome (MDS): Any 2001 WHO classification subtype (Appendix I). RAEB-2 patients may proceed directly to transplant, but may also receive induction chemotherapy before transplant. Patients with ≥20% morphologic marrow blasts will require induction therapy to reduce morphologic marrow blasts below 5% before transplant.
- High-risk AML defined as monosomy 5, del 5q, monosomy 7, M6, M7, t(6;9), FLT3-ITD, or patients who have greater than or equal to 25% blasts by morphology after induction, or who do not achieve CR after 2 courses of therapy. Also, patients with ≥ 0.1% MRD or evidence of progressive extramedullary disease after induction chemotherapy.
- AML in second or subsequent morphologic remission.
- Has not received a prior allogeneic hematopoietic stem cell transplant.
- Does not have a suitable HLA-matched sibling donor available for stem cell donation.
- Does not have a suitable matched or single antigen mismatched related or unrelated donor available at any time (noted by search), or it is in the patient's best interest as judged by the attending to move forward with stem cell transplantation rather than wait for an unrelated donor to become available (refer to subsection 2.5.1 for further details).
- Has a suitable HLA KIR favorable haploidentical matched family member available for stem cell donation.
- Karnofsky Index or Lansky Play-Performance Scale ≥ 60 % on pre-transplant evaluation. Karnofsky scores must be used for patients > 16 years of age and Lansky scores for patients < 16 years of age.
- Able to give informed consent if > 18 years, or with a legal guardian capable of giving informed consent if < 18 years.
- Adequate organ function (within 4 weeks of initiation of preparative regimen), defined as:
- Pulmonary: FEV1, FVC, and corrected DLCO must all be ≥ 50% of predicted by pulmonary function tests (PFTs). For children who are unable to perform for PFTs due to age, the criteria are: no evidence of dyspnea at rest and no need for supplemental oxygen.
- Renal: Creatinine clearance or radioisotope GFR ³ 70 mL/min/1.73 m2 or a serum creatinine based on age/gender as follows:
- Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.45
- Cardiac: Shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA) or ejection fraction of ≥ 50% by echocardiogram or radionuclide scan (MUGA), choice of test according to local standard of care.
- Hepatic: \SGOT (AST) or SGPT (ALT) < 5 x upper limit of normal (ULN) for age. Conjugated bilirubin < 2.5 mg/dL, unless attributable to Gilbert's Syndrome.
Who cannot join
- Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants.
- Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation.
- Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment are not permitted. Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible.
- Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc).
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites
Lurie Children's Hospital
Chicago, Illinois, 60611
Children's Hospital Los Angeles
Los Angeles, California, 90027
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University - Monroe Carell Jr. Children's Hospital
Nashville, Tennessee, 37232
Children's Hospital Oakland
Oakland, California, 94609
Stanford University Medical Center
Palo Alto, California, 94305
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Utah, Primary Children's Hospital
Salt Lake City, Utah, 84112
Rady Children's Hospital
San Diego, California, 92123
University of California, San Francisco
San Francisco, California, 94143
New York Medical Center
Valhalla, New York, 10595
About this study
Official title: The Role of KIR-favorably Mismatched Haploidentical Transplantation and KIR-polymorphisms in Determining Outcomes of Children With ALL/AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation
This is a phase II, open-label, non-randomized, prospective study of haploidentical transplantation using KIR-favorable donors for children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). The relationship of KIR2DL1 polymorphisms to survival in children with these diseases undergoing any approach to allogeneic HCT during the study time frame will also be determined.
Read the detailed description
Allogeneic hematopoietic stem cell transplantation (HCT) using matched related and unrelated donors is well-accepted therapy for children with subtypes of high-risk acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). For the 40-50% of children who do not have matched donors available, HCT approaches have varied by center and regional preferences. HCT physicians in France and North America tend to use human leukocyte antigen (HLA)-mismatched umbilical cord blood (UCB), while those in many large centers in Germany, parts of Asia, and selected US centers favor HLA-haploidentical donors. Both approaches have improved significantly through the years for a variety of reasons, including better supportive care, cell processing techniques that now deliver more consistently high-quality products, understanding of the importance of cell dose, and key modifications of preparative and immunosuppressive regimens.
Both stem cell sources offer distinct advantages and disadvantages. T-cell-depleted haploidentical approaches with killer-cell immunoglobulin-like receptor (KIR) mismatches have been shown to lead to less relapse in patients with AML13 and, in some studies, children with ALL as well. Disadvantages to this approach have been vulnerability to viral infection and the requirement for an ex vivo T-cell depletion procedure that is currently under IND. Cord blood is readily available and is permissive of some degree of HLA mismatch, but current studies show no advantage in survival compared with matched unrelated donors. Recently, a randomized study of one vs. two UCB units based on a hypothesis of decreased relapse incidence with two units resulted in equivalent outcomes in both arms. Neutrophil engraftment and immune recovery after UCB transplantation is relatively slow, leading to a higher risk of transplant-related mortality; in addition, larger patients require two cord units, dramatically increasing the cost of stem cell procurement. No direct comparisons of these two stem cell sources (haploidentical vs. UCB) have been performed in pediatric patients.
Recently, investigators at St. Jude Children's Research Hospital published excellent outcomes using haploidentical donors with grafts depleted for CD3+ cells by an ex vivo Miltenyi CliniMACS system. Their recent cohort of AML and ALL patients treated without total body irradiation (TBI) had a 5-year survival of 88±15% in 19 consecutive patients, with 17 surviving long-term and disease-free and only 2 patients died of progressive leukemia. These results compared favorably with the 5-year survival of 70±38% for transplantations using matched siblings and 61±17% for matched unrelated donors treated with identical leukemia protocols with indications for transplantation defined a priori. These preliminary results suggest that a strategy of using favorable KIR-mismatched haploidentical transplantation may lead to a better outcome than other alternative donor approaches without the side effects of TBI. This protocol is a phase II trial seeking to establish the feasibility and preliminary outcomes with this approach in a multi-institutional setting.
In addition to KIR-HLA matching, KIR allele polymorphism may also affect transplant outcomes.Recent data from St. Jude showed that in 312 pediatric HCTs, the patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R245) had better survival (p=0.0028) and a lower relapse rate (p=0.022) than those who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C245). Patients who received a KIR2DL1-R245-positive graft with an HLA-C receptor-ligand mismatch had the best survival (p=0.00004) and lowest risk of leukemia relapse (p=0.005). Thus, both KIR-HLA matching and KIR allele polymorphism have prognostic value. We will attempt to prospectively confirm these results in this multicenter trial.
- Being tested
- CliniMacs TCR alpha-beta-Biotin system
- Keywords
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), KIR-Favorable, Haploidentical Transplantation, Allogeneic Hematopoietic Cell Transplantation
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CliniMacs TCR alpha-beta-Biotin systemDevice
Graft ex vivo depleted of T cell receptor (TCR) αβ+CD3+/CD19+ cells
| Study group | Role | What they receive |
|---|---|---|
| KIR Favorable Transplant | Experimental | To assess in a multi-center setting whether the disease-free survival (DFS) at one-year post-HCT for children with high-risk ALL, AML and MDS can be improved following favorably KIR-mismatched haplo-HCT using a graft ex vivo depleted of T cell receptor (TCR) αβ+CD3+/CD19+ cells from CliniMacs TCR alpha-beta-Biotin system Receives: Device: CliniMacs TCR alpha-beta-Biotin system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival at 1 year post HCT
Measured: 1 year
1 yr disease free survival of patients transplanted with donors homozygous for KIR2DL1-C245 will be compared to patients with donors hetero- or homozygous for KIRD2DL1-R245 polymorphisms
Measured: 1 year
Secondary outcomes (10)
1- and 2-year overall survival (OS) for children undergoing TCR αβ+CD3+/CD19+ cell depleted favorably KIR-mismatched haplo-HCT
Measured: 2 years
Cumulative incidence of neutrophil and platelet engraftment, primary and secondary rejection, NTM, and relapse in KIR favorable haplo-HCT recipients
Measured: 1 year
Cumulative incidence of overall grades II-IV and III-IV acute GVHD in KIR favorable haplo-HCT recipients
Measured: 5 years
Compare the 2-year DFS and OS of patients transplanted using favorably KIR-mismatched haplo-HCT with other ALL, AML, and MDS patients concurrently transplanted using other approaches at the participating centers.
Measured: 1 year
Compare the 2-year DFS and OS of patients transplanted using favorably KIR-mismatched haplo-HCT with other ALL, AML, and MDS patients concurrently transplanted using 4/6 and 5/6 HLA-matched cord blood reported to the CIBMTR
Measured: 1 year
Test sensitivity of flow cytometry MRD for all patients; in ALL patients, compare flow cytometry MRD with IgH and TCR next-generation-sequencing (NGS) MRD pre- and post-HCT for predicting relapse, DFS, and OS in children undergoing allog-HCT.
Measured: 1 year
To compare costs of transplantation using favorably KIR-mismatched haplo-HCT with patients receiving alternative donor transplantation at centers participating in the trial
Measured: 1 year
1- and 2-year event free survival (DFS) for children undergoing TCR αβ+CD3+/CD19+ cell depleted favorably KIR-mismatched haplo-HCT
Measured: 2 years
Cumulative incidence of chronic GVHD in KIR favorable haplo-HCT recipients.
Measured: 1 year
Cumulative incidence of mild, moderate, and severe cGVHD
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2016 (estimated)
- Study startOct 2015
- Primary completionNov 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michael Pulsipher
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Francisco, Children's Hospital of Philadelphia, Medical College of Wisconsin, Ann & Robert H Lurie Children's Hospital of Chicago, New York Medical College, UCSF Benioff Children's Hospital Oakland, Vanderbilt University, Rady Children's Hospital, San Diego
- Responsible party
- Sponsor-investigator, Michael Pulsipher, Pediatric Transplantation & Cellular Therapy Consortium
- Investigators
- Michael Pulsipher, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02646839
- Sponsor's protocol ID
- PBMTC ONC1401
- Status last verified
- May 2025
- First submitted
- 21 Dec 2015
- Last updated
- 4 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Dvorak CC, Long-Boyle JR, Holbrook-Brown L, Abdel-Azim H, Bertaina A, Vatsayan A, Talano JA, Bunin N, Anderson E, Flower A, Lalefar N, Higham CS, Kapoor N, Klein O, Odinakachukwu MC, Cho S, Jacobsohn DA, Collier W, Pulsipher MA. Effect of rabbit ATG PK on outcomes after TCR-alphabeta/CD19-depleted pediatric haploidentical HCT for hematologic malignancy. Blood Adv. 2024 Dec 10;8(23):6003-6014. doi: 10.1182/bloodadvances.2024012670.
PubMed 39042892Pulsipher MA, Ahn KW, Bunin NJ, Lalefar N, Anderson E, Flower A, Cairo MS, Talano JA, Chaudhury S, Kitko CL, Duke JL, Monos D, Leung W, Dvorak CC, Abdel-Azim H. KIR-favorable TCR-alphabeta/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial. Blood. 2022 Dec 15;140(24):2556-2572. doi: 10.1182/blood.2022015959.
PubMed 35776909
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of KIR-favorably Mismatched Haploidentical Transplantation and KIR-polymorphisms in Determining Outcomes of Children With ALL/AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT02646839
- Acronym / sponsor ID
- PBMTC ONC1401
- Keywords
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), KIR-Favorable, Haploidentical Transplantation, Allogeneic Hematopoietic Cell Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Michael PulsipherUniversity, hospital or other
- Collaborators
- University of California, San Francisco, Children's Hospital of Philadelphia, Medical College of Wisconsin, Ann & Robert H Lurie Children's Hospital of Chicago, New York Medical College, UCSF Benioff Children's Hospital Oakland, Vanderbilt University, Rady Children's Hospital, San Diego
- Study start
- Oct 2015
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 6 Jan 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 is a phase II, open-label, non-randomized, prospective study of haploidentical transplantation using KIR-favorable donors for children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). The relationship of KIR2DL1 polymorphisms to survival in children with these diseases undergoing any approach to allogeneic HCT during the study time frame will also be determined.
Detailed description
Allogeneic hematopoietic stem cell transplantation (HCT) using matched related and unrelated donors is well-accepted therapy for children with subtypes of high-risk acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). For the 40-50% of children who do not have matched donors available, HCT approaches have varied by center and regional preferences. HCT physicians in France and North America tend to use human leukocyte antigen (HLA)-mismatched umbilical cord blood (UCB), while those in many large centers in Germany, parts of Asia, and selected US centers favor HLA-haploidentical donors. Both approaches have improved significantly through the years for a variety of reasons, including better supportive care, cell processing techniques that now deliver more consistently high-quality products, understanding of the importance of cell dose, and key modifications of preparative and immunosuppressive regimens.
Both stem cell sources offer distinct advantages and disadvantages. T-cell-depleted haploidentical approaches with killer-cell immunoglobulin-like receptor (KIR) mismatches have been shown to lead to less relapse in patients with AML13 and, in some studies, children with ALL as well. Disadvantages to this approach have been vulnerability to viral infection and the requirement for an ex vivo T-cell depletion procedure that is currently under IND. Cord blood is readily available and is permissive of some degree of HLA mismatch, but current studies show no advantage in survival compared with matched unrelated donors. Recently, a randomized study of one vs. two UCB units based on a hypothesis of decreased relapse incidence with two units resulted in equivalent outcomes in both arms. Neutrophil engraftment and immune recovery after UCB transplantation is relatively slow, leading to a higher risk of transplant-related mortality; in addition, larger patients require two cord units, dramatically increasing the cost of stem cell procurement. No direct comparisons of these two stem cell sources (haploidentical vs. UCB) have been performed in pediatric patients.
Recently, investigators at St. Jude Children's Research Hospital published excellent outcomes using haploidentical donors with grafts depleted for CD3+ cells by an ex vivo Miltenyi CliniMACS system. Their recent cohort of AML and ALL patients treated without total body irradiation (TBI) had a 5-year survival of 88±15% in 19 consecutive patients, with 17 surviving long-term and disease-free and only 2 patients died of progressive leukemia. These results compared favorably with the 5-year survival of 70±38% for transplantations using matched siblings and 61±17% for matched unrelated donors treated with identical leukemia protocols with indications for transplantation defined a priori. These preliminary results suggest that a strategy of using favorable KIR-mismatched haploidentical transplantation may lead to a better outcome than other alternative donor approaches without the side effects of TBI. This protocol is a phase II trial seeking to establish the feasibility and preliminary outcomes with this approach in a multi-institutional setting.
In addition to KIR-HLA matching, KIR allele polymorphism may also affect transplant outcomes.Recent data from St. Jude showed that in 312 pediatric HCTs, the patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R245) had better survival (p=0.0028) and a lower relapse rate (p=0.022) than those who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C245). Patients who received a KIR2DL1-R245-positive graft with an HLA-C receptor-ligand mismatch had the best survival (p=0.00004) and lowest risk of leukemia relapse (p=0.005). Thus, both KIR-HLA matching and KIR allele polymorphism have prognostic value. We will attempt to prospectively confirm these results in this multicenter trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KIR Favorable Transplant | Experimental | Device: CliniMacs TCR alpha-beta-Biotin systemTo assess in a multi-center setting whether the disease-free survival (DFS) at one-year post-HCT for children with high-risk ALL, AML and MDS can be improved following favorably KIR-mismatched haplo-HCT using a graft ex vivo depleted of T cell receptor (TCR) αβ+CD3+/CD19+ cells from CliniMacs TCR alpha-beta-Biotin system |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- 2.3.1 Inclusion Criteria for the Biology (KIR2DL1 Polymorphisms/ALL MRD), Comparative Outcomes, and Cost Effectiveness Trial
- Any patient with ALL, AML, or MDS who is deemed eligible for and undergoes HCT at participating centers who provides consent for the KIR2DL1 polymorphisms, comparative outcomes and cost-effectiveness portion of the trial.
- Any ALL patient undergoing allogeneic HCT at participating centers is eligible for the ALL deep sequence MRD portion of the trial.
- Patients ineligible for the KIR-favorable haploidentical phase II trial who require T-cell depletion may be treated using TCR αβ+CD3+/CD19+ cell depletion. These patients will be followed descriptively on this portion of the trial. Preparative regimen will be at the discretion of the transplant center, but the options associated with this protocol are recommended.
- Age < 22 years
Key exclusion criteria (4 listed)
- Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants.
- Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation.
- Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment are not permitted. Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible.
- Patients with genetic disorders (generally marrow failure syndromes) prone to secondary AML/ALL with known poor outcome are not eligible (Fanconi Anemia, Kostmann Syndrome, Dyskeratosis Congenita, etc).
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 |
|---|---|---|
| CliniMacs TCR alpha-beta-Biotin systemGraft ex vivo depleted of T cell receptor (TCR) αβ+CD3+/CD19+ cells | Device | KIR Favorable Transplant |
Primary outcome
Disease free survival at 1 year post HCT
Time frame: 1 year
1 yr disease free survival of patients transplanted with donors homozygous for KIR2DL1-C245 will be compared to patients with donors hetero- or homozygous for KIRD2DL1-R245 polymorphisms
Time frame: 1 year
10 secondary outcomes
1- and 2-year overall survival (OS) for children undergoing TCR αβ+CD3+/CD19+ cell depleted favorably KIR-mismatched haplo-HCT
Time frame: 2 years
Cumulative incidence of neutrophil and platelet engraftment, primary and secondary rejection, NTM, and relapse in KIR favorable haplo-HCT recipients
Time frame: 1 year
Cumulative incidence of overall grades II-IV and III-IV acute GVHD in KIR favorable haplo-HCT recipients
Time frame: 5 years
Compare the 2-year DFS and OS of patients transplanted using favorably KIR-mismatched haplo-HCT with other ALL, AML, and MDS patients concurrently transplanted using other approaches at the participating centers.
Time frame: 1 year
Compare the 2-year DFS and OS of patients transplanted using favorably KIR-mismatched haplo-HCT with other ALL, AML, and MDS patients concurrently transplanted using 4/6 and 5/6 HLA-matched cord blood reported to the CIBMTR
Time frame: 1 year
Test sensitivity of flow cytometry MRD for all patients; in ALL patients, compare flow cytometry MRD with IgH and TCR next-generation-sequencing (NGS) MRD pre- and post-HCT for predicting relapse, DFS, and OS in children undergoing allog-HCT.
Time frame: 1 year
To compare costs of transplantation using favorably KIR-mismatched haplo-HCT with patients receiving alternative donor transplantation at centers participating in the trial
Time frame: 1 year
1- and 2-year event free survival (DFS) for children undergoing TCR αβ+CD3+/CD19+ cell depleted favorably KIR-mismatched haplo-HCT
Time frame: 2 years
Cumulative incidence of chronic GVHD in KIR favorable haplo-HCT recipients.
Time frame: 1 year
Cumulative incidence of mild, moderate, and severe cGVHD
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
- Derived from this study: PubMed 39042892Dvorak CC, Long-Boyle JR, Holbrook-Brown L, Abdel-Azim H, Bertaina A, Vatsayan A, Talano JA, Bunin N, Anderson E, Flower A, Lalefar N, Higham CS, Kapoor N, Klein O, Odinakachukwu MC, Cho S, Jacobsohn DA, Collier W, Pulsipher MA. Effect of rabbit ATG PK on outcomes after TCR-alphabeta/CD19-depleted pediatric haploidentical HCT for hematologic malignancy. Blood Adv. 2024 Dec 10;8(23):6003-6014. doi: 10.1182/bloodadvances.2024012670.
- Derived from this study: PubMed 35776909Pulsipher MA, Ahn KW, Bunin NJ, Lalefar N, Anderson E, Flower A, Cairo MS, Talano JA, Chaudhury S, Kitko CL, Duke JL, Monos D, Leung W, Dvorak CC, Abdel-Azim H. KIR-favorable TCR-alphabeta/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial. Blood. 2022 Dec 15;140(24):2556-2572. doi: 10.1182/blood.2022015959.
- Individual participant dataSharing planned: No
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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.
Michael Pulsipher, MD principal investigator
Children's Hospital Los Angeles
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CliniMacs TCR alpha-beta-Biotin system in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Michael Pulsipher at 11 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 25 inclusion and 4 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: enrolling by invitation, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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 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?
This study is still under way. Results are not available in the source record yet.
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?
Disease free survival at 1 year post HCT (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT02646839, which also lists 2 linked publications.
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 4 May 2025.