Acute LeukemiaNCT01598025
Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
A study testing total-body irradiation (TBI), thiotepa and fludarabine phosphate in people with Acute Leukemia and Chronic Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors. Read more about this study
- Who is it for?
- Ages Up to 19 years
- Conditions the study is for
- Acute Leukemia, Chronic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- total-body irradiation (TBI), thiotepa and fludarabine phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2012to 16 Oct 2017
- Phase
- Interventional
- 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 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Malignant conditions for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
- AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16).
- Secondary AML in 1st remission
- AML in 1st relapse or > 2nd remission
- ALL/LL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL > 2nd remission
- CML failing to respond to or not tolerating Imatinib, dasatinib, or nilotinib in first chronic phase of disease; or CML in accelerated phase or second chronic phase.
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- Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories: a) intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
- any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant. Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation under protocol IRB 08-008.
- Chronic myelomonocytic leukemia: CMML-1 and CMML-2.
- Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or conjugated cytopenias; non-SCID lethal genetic immunodeficiencies such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, ALPS).
- Patients may be of either gender and of any racial or ethnic background.
- Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > 70%.
- Patients must have adequate organ function measured by:
- Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.
- Hepatic: < 3x ULN ALT and < 2.0x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
- Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated)
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
Who cannot join
- Female patients who are pregnant or breast-feeding
- Uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
- Presence of leukemia in the CNS.
- Donor Inclusion Criteria:
- Each donor must meet criteria outlined by institutional policies
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- Donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter.
- Donor Exclusion Criteria:
- Evidence of active infection (including urinary tract infection, or upper respiratory tract infection), viral hepatitis exposure (on screening), unless only HBS Ab+ and HBV DNA negative, or serologic evidence of exposure or infection with HIV-I/II or HTLV-I/II
- If donors do not meet institutional guidelines, exclusion will be considered.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065-0009
About this study
Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors.
This study is being done to test the safety and the treatment results of a specific kind of transplant. In this transplant, blood from two donors will be used. Each donor will share one half of your HLA type. Blood from both donors will be transplanted at the same time.
- Being tested
- total-body irradiation (TBI), thiotepa, fludarabine phosphate, melphalan, anti-thymocyte globulin
- Keywords
- ANTITHYMOCYTE GLOBULIN:ATG, FLUDARABINE, THI0TEPA, CliniMACS-CD34 Reagent System, 12-053
- Medical subject headings
- Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
total-body irradiation (TBI)Radiation
thiotepaDrug
melphalanDrug
anti-thymocyte globulinBiological
allogeneic hematopoietic stem cell transplantationProcedure or surgery
laboratory biomarker analysisOther
| Study group | Role | What they receive |
|---|---|---|
| REGIMEN 1 | Experimental | REGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2.
TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. Receives: Radiation: total-body irradiation (TBI); Drug: thiotepa; Drug: fludarabine phosphate; Biological: anti-thymocyte globulin; Procedure: allogeneic hematopoietic stem cell transplantation; Biological: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis |
| Regimen 2 | Experimental | To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days.
TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. Receives: Drug: thiotepa; Drug: fludarabine phosphate; Drug: melphalan; Biological: anti-thymocyte globulin; Procedure: allogeneic hematopoietic stem cell transplantation; Biological: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants
Efficacy is measured by:
- incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant.
- incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure
- incidence and severity of acute and/or chronic GVHD
- incidence and severity of opportunistic infections developing following engraftment
Measured: 1 year
Secondary outcomes (1)
Evaluation of Recipients Post Transplant
The levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post transplant. The tolerance or reactivity of engrafted T cells from each donor detected in the blood at 3, 6, and thereafter every 3-6 months until normal, post transplant against host cells and cells derived from the other parent as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays.
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 posted15 May 2012 (estimated)
- Study start2 May 2012
- Primary completion16 Oct 2017
- Study completion16 Oct 2017
Why it stopped: Closed due to poor accrual
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.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard O'Reilly, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01598025
- Sponsor's protocol ID
- 12-053
- Status last verified
- Jul 2018
- First submitted
- 9 May 2012
- Last updated
- 9 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
- ClinicalTrials.gov ID
- NCT01598025
- Acronym / sponsor ID
- 12-053
- Keywords
- ANTITHYMOCYTE GLOBULIN:ATG, FLUDARABINE, THI0TEPA, CliniMACS-CD34 Reagent System, 12-053
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed due to poor accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 2 May 2012 (actual)
- Primary completion
- 16 Oct 2017 (actual)
- Study completion
- 16 Oct 2017 (actual)
- First posted
- 15 May 2012 (estimated)
- Results
- Posted 17 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 30% of patients who are candidates for bone marrow transplants do not have an HLA-matched, or close to matched, donor available. For this reason, doctors have been testing ways to make transplants from HLA-partially matched donors as safe and effective as transplants from HLA-matched donors.
This study is being done to test the safety and the treatment results of a specific kind of transplant. In this transplant, blood from two donors will be used. Each donor will share one half of your HLA type. Blood from both donors will be transplanted at the same time.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| REGIMEN 1 | Experimental | Radiation: total-body irradiation (TBI), Drug: thiotepa, Drug: fludarabine phosphate, Biological: anti-thymocyte globulin, Procedure: allogeneic hematopoietic stem cell transplantation, Biological: peripheral blood stem cell transplantation, Other: laboratory biomarker analysisREGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. |
| Regimen 2 | Experimental | Drug: thiotepa, Drug: fludarabine phosphate, Drug: melphalan, Biological: anti-thymocyte globulin, Procedure: allogeneic hematopoietic stem cell transplantation, Biological: peripheral blood stem cell transplantation, Other: laboratory biomarker analysisTo be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. |
Who may qualify
- Ages
- Up to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Malignant conditions for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
- AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16).
- Secondary AML in 1st remission
- AML in 1st relapse or > 2nd remission
- ALL/LL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL > 2nd remission
Key exclusion criteria (10 listed)
- Female patients who are pregnant or breast-feeding
- Uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
- Presence of leukemia in the CNS.
- Each donor must meet criteria outlined by institutional policies
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-body irradiation (TBI) | Radiation | REGIMEN 1 |
| thiotepa | Drug | REGIMEN 1, Regimen 2 |
| fludarabine phosphate | Drug | REGIMEN 1, Regimen 2 |
| melphalan | Drug | Regimen 2 |
| anti-thymocyte globulin | Biological | REGIMEN 1, Regimen 2 |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | REGIMEN 1, Regimen 2 |
| peripheral blood stem cell transplantation | Biological | REGIMEN 1, Regimen 2 |
| laboratory biomarker analysis | Other | REGIMEN 1, Regimen 2 |
Primary outcome
Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants
Time frame: 1 year
Efficacy is measured by: 1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant. 2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure 3. incidence and severity of acute and/or chronic GVHD 4. incidence and severity of opportunistic infections developing following engraftment
1 secondary outcome
Evaluation of Recipients Post Transplant
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink 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.
Richard O'Reilly, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing total-body irradiation (TBI), thiotepa and fludarabine phosphate in people with Acute Leukemia and Chronic Leukemia, run by Memorial Sloan Kettering Cancer Center 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 18 inclusion and 10 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: stopped early, as of the sponsor's last update on 9 Aug 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2018). 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?
Efficacy of HLA-haploidentical Biparental T-cell Depleted CD34+ Peripheral Blood Stem Cell Transplants (time frame: 1 year). 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 9 Aug 2018.