Acute Lymphoblastic Leukemia (ALL)Phase 2NCT02790515
Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation
A Phase 2 study testing Anti-thymocyte globulin (rabbit), Blinatumomab and Cyclophosphamide in people with Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myeloid Sarcoma
- What is being tested?
- Anti-thymocyte globulin (rabbit), Blinatumomab and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jul 2016to 1 Jul 2026
- Phase
- Phase 2
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.
- Any of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic HCT (this includes any stage of disease - such as refractory due to induction failure, refractory in relapse, or in any CR - as long as the hematologic malignancy remained persistent or returned after a previous allogeneic HCT):
- ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)
- Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
- Does not have any other active malignancy other than the one for which this transplant is indicated.
- If prior CNS leukemia, it must be treated and in CNS CR
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- Does not have current uncontrolled bacterial, fungal, or viral infection.
- There is no minimum time from the previous transplant, but patients must meet the following criteria:
- Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%.
- Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.
- Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing.
- Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See Appendix A).
- Bilirubin ≤ 3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.
- Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
- Not breast feeding
- 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 donation eligibility, is identified as either:
- Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- 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
This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation.
PRIMARY OBJECTIVE:
Read more
- To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation.
SECONDARY OBJECTIVES:
- Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy.
- 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
Blood progenitor cells will be obtained from a partially matched adult family member (donor). After processing and filtration using the CliniMACS device, cells will be infused into participants meeting eligibility criteria.
Prior to transplant, participants will receive a conditioning treatment of rabbit ATG, cyclophosphamide, fludarabine, thiotepa, melphalan, and rituximab. Mesna will be given to help prevent side effects of cyclophosphamide. Tacrolimus will be given to help reduce the risk of GVHD. G-CSF will be given after transplant to help the donor progenitor cells make white blood cells faster so that the immune system is better able to fight infection.
Blood progenitor cells will be given in two infusions on Day 0 and Day +1. Progenitor cells then move through the blood stream to the bone marrow space where they should begin to grow. Participant blood will be monitored for 100 days to assure that the progenitor cells begin to grow. If the growth is low, additional progenitor cells may be given.
Blood tests will be monitored for up to one year to observe how well the donor cells grow and their effect on the infection-fighting system.
- Conditions
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Myeloid Sarcoma, Chronic Myeloid Leukemia (CML), Juvenile Myelomonocytic Leukemia (JMML), Myelodysplastic Syndrome (MDS)
- Being tested
- Anti-thymocyte globulin (rabbit), Blinatumomab, Cyclophosphamide, Fludarabine, G-CSF
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Sarcoma, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Juvenile, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-thymocyte globulin (rabbit)Drug
Also called Thymoglobulin®, rabbit ATG
Given intravenous (IV) prior to transplant on Days -14, -13, -12.
BlinatumomabDrug
Also called Blincyto
Given by continuous IV infusion at least 2 weeks post-engraftment. Blinatumomab will be given only to patients with CD19+ malignancies.
CyclophosphamideDrug
Also called Cytoxan
Given by IV infusion prior to transplant on Day -9.
FludarabineDrug
Also called Fludara
Given IV prior to transplant on Days -8, -7, -6, -5, and -4.
G-CSFDrug
Also called Filgrastim, Neupogen®
Given IV or subcutaneous (SQ) following transplant on Days 6 and 7.
MelphalanDrug
Also called L-phenylalanine mustard, Phenylalanine mustard, L-PAM, L-sarcolysin
Given IV prior to transplant on Days -2 and -1.
MesnaDrug
Also called Mesnex
Given IV prior to cyclophosphamide administration and at approximately 3, 6, and 9 hours after cyclophosphamide infusion.
RituximabDrug
Also called Rituxan™
Given IV prior to transplant on Day -1.
TacrolimusDrug
Also called FK506, Prograf®, Protopic®
Given oral (PO) or IV beginning prior to transplant on Day -2. The dose will begin to taper at approximately day +60 after transplant in the absence of GVHD. Tacrolimus was used for the first 5 participants enrolled on study. Subsequent participants receive sirolimus.
ThiotepaDrug
Also called Thioplex® by Immunex, TESPA, TSPA
Given IV prior to transplant on Day -3.
HPC,A InfusionBiological
Also called Transplant
Hematopoietic Progenitor Cell, Apheresis (HPC,A) infusion of TCRɑβ+ depleted cells on day of transplant (Day 0) and HPC,A infusion of CD45RA+ depleted cells on Day +1 following transplant.
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.
SirolimusDrug
Also called Rapamycin, Rapamune®
Given orally (PO) starting Day 0. The dose will be tapered off over two weeks starting on Day +42 in the absence of GVHD.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants receive a conditioning regimen of antithymocyte globulin (rabbit), cyclophosphamide, mesna, fludarabine, thiotepa, tacrolimus (first 5 participants enrolled), sirolimus (used beginning with 6th enrolled participant), melphalan, rituximab. This is followed by HPC,A infusion (transplant), then by G-CSF and blinatumomab.
Cells for infusion are prepared using the CliniMACS System. Receives: Drug: Anti-thymocyte globulin (rabbit); Drug: Blinatumomab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: G-CSF; Drug: Melphalan; Drug: Mesna; Drug: Rituximab; Drug: Tacrolimus; Drug: Thiotepa; Biological: HPC,A Infusion; Device: CliniMACS; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of patients engrafted by day +30 post-transplant
ANC engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm^3 with evidence of donor cell engraftment.
Measured: 30 days post-transplant
Secondary outcomes (4)
The number of patients experiencing Blinatumomab permanent discontinuation due to toxicity
If the drug is held for more than 2 weeks due to toxicity, it will be permanently discontinued.
Measured: 3 months post-transplant
The estimate of cumulative incidence of relapse
The estimate of cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. The Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) along with their standard errors will be calculated.
OS is defined as time from transplantation to death or last follow-up, whichever comes first. EFS is defined as time from transplantation to events including relapse, graft failure, death due to any cause and last follow-up whichever comes first. The participants surviving at the time of analysis without events will be censored.
Measured: One year post-transplant
The cumulative incidence of acute and chronic Graft-Versus-Host Disease (GVHD)
The cumulative incidence of acute and chronic GVHD will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event. GVHD will be reported separately for participants receiving tacrolimus and those receiving sirolimus.
The severity of acute GVHD and chronic GVHD will be described.
Measured: One year post transplant
The cumulative incidence of transplant related mortality
The cumulative incidence of transplant related mortality will be estimated using Kalbfleisch-Prentice method. Deaths before day 100 because of other reasons are the competing risk events.
Measured: 100 days post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study start14 Jul 2016
- Primary completion1 Jul 2025
- Study completion1 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia (ALL)Studies 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
- 170 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brandon Triplett, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02790515
- Sponsor's protocol ID
- REF2HCT
- Other IDs
- NCI-2016-00812
- Status last verified
- Aug 2025
- First submitted
- 31 May 2016
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes