Leukemia, Myeloid, AcuteNCT00859586
Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation
A study testing Miltenyi Magnetic cell sorter for CD3 in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Patients receiving allogeneic stem cell transplantation for hematological malignancies who suffer a relapse of their disease post-transplant have limited treatment options and a poor prognosis. Read more about this study
- Who is it for?
- Ages 8 to 75 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Leukemia, Lymphoblastic, Acute, Leukemia, Myelocytic, Chronic
- What is being tested?
- Miltenyi Magnetic cell sorter for CD3
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Sep 2014
- 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 8 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosed with one of the following hematological conditions:
- Acute lymphoblastic leukemia (ALL) of any subtype or
- Acute myelogenous leukemia (AML) of any subtype or
- Myelodysplastic syndrome (MDS) of any subtype or
- Blastic phase Chronic Myeloid Leukemia (CML)
- Relapsed disease within 6 months of matched sibling allogeneic stem cell transplant procedure
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- Evaluation for protocol within 8 weeks of relapse and enrollment within 12 weeks or relapse
- 8-75 years of age
- Availability of previous HLA identical (6/6) related donor (ages 8 to 17 must have previously donated bone marrow [not peripheral blood]
- At least one haploidentical (1-3 antigen mismatched) related donor available for apheresis
- HLA-matched sibling stem cell donor from the original transplant to participate in a stem cell rescue only in the setting of severe, refractory GvHD caused by the haploidentical cells.
- Related HLA haplo-identical (1-3 A, B or DR antigens mismatched with recipient). To maximize the GvL that is associated with HLA disparity, the haploidentical donor will be chosen based on the greatest HLA mismatch (preference: 3/6 greater than 4/6 greater than 5/6). Parents and siblings will be considered equally.
- Weight greater than or equal to 18 kg
- Age greater than or equal to 8 or less than or equal to 80 years old.
- Related HLA haplo-identical (1-3 A, B or DR antigens mismatched with recipient). To maximize the GvL that is associated with HLA disparity, the haploidentical donor will be chosen based on the greatest HLA mismatch (preference: 3/6 greater than 4/6 greater than 5/6). Donors age less than 80 years required, and parents and siblings will be considered equally.
- Age greater than or equal to 18 or less than or equal to 80 years old.
- Exclusion Criteria Haplo Lymphocyte Donor (any of the following):
- Pregnant or lactating
- Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
- Sickling hemoglobinopathies such as HbSS and HbSC .
- HIV positive. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II), or T.cruzi (Chagas) will be used at the discretion of the investigator following counseling and approval from the recipient.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and/or informed consent impossible
Who cannot join
- Active grade II-IV Graft vs. Host Disease (GvHD)
- Extensive chronic Graft vs. Host Disease (GvHD)
- Post-transplant donor lymphocyte infusion (DLI) from original donor within 1 month of protocol enrollment.
- Progressive disease despite post-relapse chemo or monoclonal therapy.
- Co-morbidity of such severity that it would preclude the patients ability to tolerate protocol therapy.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 10 x ULN (grade 3, CTCAE).
Show all 17Show fewer
- Bilirubin greater than 5 x Upper Limit of Normal (ULN) (grade 3, CTCAE).
- Creatinine greater than 3.5 mg/dl (grade 3, CTCAE).
- HIV positive (Recipients who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) are not excluded from participation).
- Positive pregnancy test for women of childbearing age.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible.
- Pregnant or lactating
- Unfit to receive filgrastim (G-CSF) or previous filgrastim mobilization for donors under 18 years of age.
- Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension).
- Sickling hemoglobinopathies such as HbSS or HbSC.
- HIV positive. Donors who are positive for hepatitis B (HBV), hepatitis C (HCV), human T-cell lymphotropic virus (HTLV-I/II), or T.cruzi (Chagas) will be used at the discretion of the investigator following counseling and approval from the recipient.
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and/or informed consent impossible.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health
Bethesda, Maryland, 20852
About this study
Patients receiving allogeneic stem cell transplantation for hematological malignancies who suffer a relapse of their disease post-transplant have limited treatment options and a poor prognosis. With the exception of patients with chronic leukemias who may achieve prolonged remissions after donor lymphocyte infusions (DLIs), treatments using either chemotherapy or a DLI achieve less than a 10% median survival beyond 6 months. Most of these patients die of progressive leukemia, underlying the need for new therapeutic approaches.
Human leukocyte antigen (HLA)-mismatched DLIs appear to possess a more potent graft-versus-leukemia (GvL) effect. However, when given after an HLA-mismatched transplant DLIs have a high risk of causing graft-versus-host disease (GvHD), which can be severe. To reduce the risk of GvHD, infusions of mismatched lymphocytes from an alternative donor may be used to avoid permanent engraftment and associated risk of GvHD.
In this study, we propose to use a novel strategy to treat leukemias relapsing after HLA matched allogeneic stem cell transplantation by using haplo-identical DLIs to promote the associated antileukemic effect while minimizing the possibility of permanent engraftment and associated GvHD. To achieve only temporary engraftment and to promote disease control we will give fludarabine immunosuppression prior to the DLI. We anticipate the infusion of HLA-mismatched donor lymphocytes in this setting will produce no detectible engraftment or only temporary engraftment, but may result in a strong GvL effect regardless of engraftment outcome. We will select patients for this protocol who fall into the worst category for post-transplant relapse. Specifically, we will enroll patients with acute leukemia or MDS relapsing within 6 months of transplant, of which less than 5% survive beyond a year from relapse.
Read the detailed description
Patients receiving allogeneic stem cell transplantation for hematological malignancies who suffer a relapse of their disease post-transplant have limited treatment options and a poor prognosis. With the exception of patients with chronic leukemias who may achieve prolonged remissions after donor lymphocyte infusions (DLIs), treatments using either chemotherapy or a DLI achieve less than a 10% median survival beyond 6 months. Most of these patients die of progressive leukemia, underlying the need for new therapeutic approaches.
HLA-mismatched DLIs appear to possess a more potent graft-versus-leukemia (GvL) effect. However, when given after an HLA-mismatched transplant DLIs have a high risk of causing graft-versus-host disease (GvHD), which can be severe. To reduce the risk of GvHD, infusions of mismatched lymphocytes from an alternative donor may be used to avoid permanent engraftment and associated risk of GvHD.
In this study, we propose to use a novel strategy to treat leukemias relapsing after HLA matched allogeneic stem cell transplantation by using haplo-identical DLIs to promote the associated antileukemic effect while minimizing the possibility of permanent engraftment and associated GvHD. To achieve only temporary engraftment and to promote disease control we will give fludarabine immunosuppression prior to the DLI. We anticipate the infusion of HLA-mismatched donor lymphocytes in this setting will produce no detectible engraftment or only temporary engraftment, but may result in a strong GvL effect regardless of engraftment outcome. We will select patients for this protocol who fall into the worst category for post-transplant relapse. Specifically, we will enroll patients with acute leukemia or MDS relapsing within 6 months of transplant, of which less than 5% survive beyond a year from relapse.
The primary objective of this phase II clinical trial will be to evaluate the safety and efficacy of using a non-engraftment model and a lymphocytes infusion from a haplo-identical donor to treat relapsed disease following matched sibling stem cell transplantation in subjects who are not candidates for alternative treatment options.
We therefore propose this is a phase II clinical trial is to evaluate the safety and efficacy of an infusion of unmanipulated lymphocytes from a haplo-identical donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options.
The primary endpoint of this phase 2 study is survival at 6 month post-relapse of disease. Successful outcome of the study will be a survival of 100% greater than the National Heart Lung and Blood (NHLBI) historical 25% at 6-months.
Secondary endpoints will include: incidence and severity of induced GvHD, proportion of DLI engraftment, peak chimerism, leukemia response at 21 days post DLI, residual leukemia measured by patient chimerism, leukemia free survival from date relapse, and safety of the mismatched DLI procedure.
- Being tested
- Miltenyi Magnetic cell sorter for CD3
- Keywords
- Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL, Myelodysplastic Syndrome, MDS
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Lymphocytic, Chronic, B-Cell, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Miltenyi Magnetic cell sorter for CD3Device
Also called CliniMACS Miltenyi
Receipts will receive 1 x 10 to eighth power CD3 cells/kg of familial haploidentical positively selected cluster of differentiation 34 (CD34)+ stem cells from the same DLI donor.
| Study group | Role | What they receive |
|---|---|---|
| Miltenyi Magnetic cell sorter for CD3 | Experimental | Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg.
This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease. Receives: Device: Miltenyi Magnetic cell sorter for CD3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Recipient Survival at 6-month Post-relapse of Disease
This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
Measured: 6 months post-relapse of disease
Secondary outcomes (10)
Number of Participants Who Developed of Acute GVHD
Overall number incidences of participants who developed Acute Graft versus Host Disease (GVHD).
Measured: 6 months post disease relapse
Number of Participants Who Developed Grade I, Acute GVHD
Number of participants who developed Grade I, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Grade 1 is defined as: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day.
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 6 months post disease relapse
Number of Participants Who Developed Grade II, Acute GVHD
Number of participants who developed Grade II, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Stage II Acute GVHD: Skin - rash on 25-50 percent body surface area; Liver - Total Bilirubin 3.1-6.0 mg/dL; Lower GI - Diarrhea 1001-1500 mL/day.
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 6 months post disease relapse
Number of Participants Who Developed Grade III, Acute GVHD
Number of participants who developed Grade III, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Stage III Acute GVHD: Skin - Rash on >50% of body surface; Liver - Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI - Diarrhea > 1500 mL/day Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 6 months post disease relapse
Number of Participants Who Developed of Grade IV, Acute GVHD
Number of participants who developed Grade IV, Acute Graft vs Host Disease (GVHD) as defined by CIMBTR criteria for Organ Stages of Acute GVHD.
Grade IV, Acute GVHD is defined as: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus.
Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: 6 months post disease relapse
Number of Participants Who Developed Chronic GVHD
Number of incidences of participants who developed Chronic Graft vs Host Disease (GVHD). Moderate GVHD is 3 or more organs with score 1, any organ with score 2, or lung with score 1, and usually requires systemic immune-suppressive treatment. Mild disease is associated with a good prognosis whereas severe disease is associated with higher treatment-related mortality and lower survival.
Organs are scored on a 0 to 3 scale from no involvement/no symptoms to severe functional compromise.
Measured: 6 months post disease relapse
Number of Participants Who Developed Limited Chronic GVHD
Number of participants who developed Limited Chronic Graft vs Host Disease (GVHD). Limited chronic GVHD is defined as GVHD occurring after day 100 that involved localized skin and/or mouth and/or liver.
Measured: 6 months post disease relapse
Number of Participants With Extensive, Chronic GVHD
Number of participants with extensive, Chronic Graft vs Host Disease (GVHD). Extensive chronic GVHD is defined as GVHD occurring after day 100 that did not meet the definition of limited chronic GVHD.
Measured: 6 months post disease relapse
Number of Participants With CD3+ Engraftment Who Achieved Peak Chimerism Post DLI
Number of Participants with CD3+ Engraftment who Achieved Peak Chimerism post Donor Lymphocyte Infusion (DLI)
Measured: 21 Days
Number of Subjects Leukemia Response After Donor Lymphocyte Infusion (DLI)
Subjects experience leukemia response after partially human leukocyte antigen (HLA) matched DLI according to International Working Group criteria
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionSep 2014
- Study completionSep 2014
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 (3)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Not applicable
- Intervention model
- Single group
- Model description
- The CliniMACS CD34 Reagent System is a medical device used in vitro to select and enrich specific cell populations (CD34+ cells from heterogeneous hematological cell populations). In stage 1, subjects will receive 1 x 108 CD3 cells/kg on day 0. We will progress to stage 2 where the dose of CD3+ cells will be increased to 2 x 108 cells/kg.
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Minoo Battiwalla, Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00859586
- Sponsor's protocol ID
- 090087
- Other IDs
- 09-H-0087
- Status last verified
- Aug 2014
- First submitted
- 10 Mar 2009
- Last updated
- 27 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.
PubMed 8114836Montero A, Savani BN, Shenoy A, Read EJ, Carter CS, Leitman SF, Mielke S, Rezvani K, Childs R, Barrett AJ. T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biol Blood Marrow Transplant. 2006 Dec;12(12):1318-25. doi: 10.1016/j.bbmt.2006.08.034.
PubMed 17162214Levine JE, Braun T, Penza SL, Beatty P, Cornetta K, Martino R, Drobyski WR, Barrett AJ, Porter DL, Giralt S, Leis J, Holmes HE, Johnson M, Horowitz M, Collins RH Jr. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002 Jan 15;20(2):405-12. doi: 10.1200/JCO.2002.20.2.405.
PubMed 11786567
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00859586
- Acronym / sponsor ID
- 090087
- Keywords
- Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia, AML, Acute Lymphoblastic Leukemia, ALL
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Feb 2009
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 11 Mar 2009 (estimated)
- Results
- Posted 6 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients receiving allogeneic stem cell transplantation for hematological malignancies who suffer a relapse of their disease post-transplant have limited treatment options and a poor prognosis. With the exception of patients with chronic leukemias who may achieve prolonged remissions after donor lymphocyte infusions (DLIs), treatments using either chemotherapy or a DLI achieve less than a 10% median survival beyond 6 months. Most of these patients die of progressive leukemia, underlying the need for new therapeutic approaches.
Human leukocyte antigen (HLA)-mismatched DLIs appear to possess a more potent graft-versus-leukemia (GvL) effect. However, when given after an HLA-mismatched transplant DLIs have a high risk of causing graft-versus-host disease (GvHD), which can be severe. To reduce the risk of GvHD, infusions of mismatched lymphocytes from an alternative donor may be used to avoid permanent engraftment and associated risk of GvHD.
In this study, we propose to use a novel strategy to treat leukemias relapsing after HLA matched allogeneic stem cell transplantation by using haplo-identical DLIs to promote the associated antileukemic effect while minimizing the possibility of permanent engraftment and associated GvHD. To achieve only temporary engraftment and to promote disease control we will give fludarabine immunosuppression prior to the DLI. We anticipate the infusion of HLA-mismatched donor lymphocytes in this setting will produce no detectible engraftment or only temporary engraftment, but may result in a strong GvL effect regardless of engraftment outcome. We will select patients for this protocol who fall into the worst category for post-transplant relapse. Specifically, we will enroll patients with acute leukemia or MDS relapsing within 6 months of transplant, of which less than 5% survive beyond a year from relapse.
Detailed description
Patients receiving allogeneic stem cell transplantation for hematological malignancies who suffer a relapse of their disease post-transplant have limited treatment options and a poor prognosis. With the exception of patients with chronic leukemias who may achieve prolonged remissions after donor lymphocyte infusions (DLIs), treatments using either chemotherapy or a DLI achieve less than a 10% median survival beyond 6 months. Most of these patients die of progressive leukemia, underlying the need for new therapeutic approaches.
HLA-mismatched DLIs appear to possess a more potent graft-versus-leukemia (GvL) effect. However, when given after an HLA-mismatched transplant DLIs have a high risk of causing graft-versus-host disease (GvHD), which can be severe. To reduce the risk of GvHD, infusions of mismatched lymphocytes from an alternative donor may be used to avoid permanent engraftment and associated risk of GvHD.
In this study, we propose to use a novel strategy to treat leukemias relapsing after HLA matched allogeneic stem cell transplantation by using haplo-identical DLIs to promote the associated antileukemic effect while minimizing the possibility of permanent engraftment and associated GvHD. To achieve only temporary engraftment and to promote disease control we will give fludarabine immunosuppression prior to the DLI. We anticipate the infusion of HLA-mismatched donor lymphocytes in this setting will produce no detectible engraftment or only temporary engraftment, but may result in a strong GvL effect regardless of engraftment outcome. We will select patients for this protocol who fall into the worst category for post-transplant relapse. Specifically, we will enroll patients with acute leukemia or MDS relapsing within 6 months of transplant, of which less than 5% survive beyond a year from relapse.
The primary objective of this phase II clinical trial will be to evaluate the safety and efficacy of using a non-engraftment model and a lymphocytes infusion from a haplo-identical donor to treat relapsed disease following matched sibling stem cell transplantation in subjects who are not candidates for alternative treatment options.
We therefore propose this is a phase II clinical trial is to evaluate the safety and efficacy of an infusion of unmanipulated lymphocytes from a haplo-identical donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options.
The primary endpoint of this phase 2 study is survival at 6 month post-relapse of disease. Successful outcome of the study will be a survival of 100% greater than the National Heart Lung and Blood (NHLBI) historical 25% at 6-months.
Secondary endpoints will include: incidence and severity of induced GvHD, proportion of DLI engraftment, peak chimerism, leukemia response at 21 days post DLI, residual leukemia measured by patient chimerism, leukemia free survival from date relapse, and safety of the mismatched DLI procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The CliniMACS CD34 Reagent System is a medical device used in vitro to select and enrich specific cell populations (CD34+ cells from heterogeneous hematological cell populations). In stage 1, subjects will receive 1 x 108 CD3 cells/kg on day 0. We will progress to stage 2 where the dose of CD3+ cells will be increased to 2 x 108 cells/kg.
| Arm | Type | Receives |
|---|---|---|
| Miltenyi Magnetic cell sorter for CD3 | Experimental | Device: Miltenyi Magnetic cell sorter for CD3Miltenyi Magnetic cell sorter device will be used for CD3 selection of granulocyte colony stimulating factor mobilized allogeneic PBSCT. In stage 1, subjects will receive 1 x 10 to the eight power CD3 cells/kg. In stage II, the dose of CD3+ cells will be increased to 2 x 10 to the eight power cells/kg. This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease. |
Who may qualify
- Ages
- 8 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- Diagnosed with one of the following hematological conditions:
- Relapsed disease within 6 months of matched sibling allogeneic stem cell transplant procedure
- Evaluation for protocol within 8 weeks of relapse and enrollment within 12 weeks or relapse
- 8-75 years of age
- Availability of previous HLA identical (6/6) related donor (ages 8 to 17 must have previously donated bone marrow [not peripheral blood]
Key exclusion criteria (17 listed)
- Active grade II-IV Graft vs. Host Disease (GvHD)
- Extensive chronic Graft vs. Host Disease (GvHD)
- Post-transplant donor lymphocyte infusion (DLI) from original donor within 1 month of protocol enrollment.
- Progressive disease despite post-relapse chemo or monoclonal therapy.
- Co-morbidity of such severity that it would preclude the patients ability to tolerate protocol therapy.
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 |
|---|---|---|
| Miltenyi Magnetic cell sorter for CD3Also: CliniMACS MiltenyiReceipts will receive 1 x 10 to eighth power CD3 cells/kg of familial haploidentical positively selected cluster of differentiation 34 (CD34)+ stem cells from the same DLI donor. | Device | Miltenyi Magnetic cell sorter for CD3 |
Primary outcome
Overall Recipient Survival at 6-month Post-relapse of Disease
Time frame: 6 months post-relapse of disease
This phase II clinical trial is designed to evaluate a novel non-myeloablative but highly immunosuppressive disease specific conditioning regimen and infusion of unmanipulated lymphocytes from a haplo-identical familial donor in subjects with relapsed disease following matched sibling stem cell transplantation who are not candidates for alternative treatment options. The clinical trial will evaluate recipient survival at six months post-relapse of disease.
10 secondary outcomes
Number of Participants Who Developed of Acute GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed Grade I, Acute GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed Grade II, Acute GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed Grade III, Acute GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed of Grade IV, Acute GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed Chronic GVHD
Time frame: 6 months post disease relapse
Number of Participants Who Developed Limited Chronic GVHD
Time frame: 6 months post disease relapse
Number of Participants With Extensive, Chronic GVHD
Time frame: 6 months post disease relapse
Number of Participants With CD3+ Engraftment Who Achieved Peak Chimerism Post DLI
Time frame: 21 Days
Number of Subjects Leukemia Response After Donor Lymphocyte Infusion (DLI)
Time frame: 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8114836Armitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available.
- Background: PubMed 17162214Montero A, Savani BN, Shenoy A, Read EJ, Carter CS, Leitman SF, Mielke S, Rezvani K, Childs R, Barrett AJ. T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome. Biol Blood Marrow Transplant. 2006 Dec;12(12):1318-25. doi: 10.1016/j.bbmt.2006.08.034.
- Background: PubMed 11786567Levine JE, Braun T, Penza SL, Beatty P, Cornetta K, Martino R, Drobyski WR, Barrett AJ, Porter DL, Giralt S, Leis J, Holmes HE, Johnson M, Horowitz M, Collins RH Jr. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002 Jan 15;20(2):405-12. doi: 10.1200/JCO.2002.20.2.405.
- NIH Clinical Center Detailed Web PageLink 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.
Minoo Battiwalla principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Miltenyi Magnetic cell sorter for CD3 in people with Leukemia, Myeloid, Acute and Leukemia, Lymphoblastic, Acute, run by National Heart, Lung, and Blood Institute (NHLBI) 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 22 inclusion and 17 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 27 Oct 2020. 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 6 Nov 2015). 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?
Overall Recipient Survival at 6-month Post-relapse of Disease (time frame: 6 months post-relapse of disease). 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 NCT00859586, which also lists 3 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 27 Oct 2020.