N/A
N=8
Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation
Leukemia, Myeloid, Acute · Leukemia, Lymphoblastic, Acute · Leukemia, Myelocytic, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT00859586 ↗Enrolled (actual)
8
Serious AEs
100.0%
Results posted
Nov 2015
Primary outcome: Primary: Overall Recipient Survival at 6-month Post-relapse of Disease — 0; 4 participants
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Miltenyi Magnetic cell sorter for CD3 (Device)
- Age
- Pediatric, Adult, Older Adult · 8+ yrs
- Sex
- All
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Primary completion
- Sep 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Recipient Survival at 6-month Post-relapse of Disease |
0; 4 | — |
| SECONDARY Number of Participants Who Developed of Acute GVHD |
2 | — |
| SECONDARY Number of Participants Who Developed Grade I, Acute GVHD |
1 | — |
| SECONDARY Number of Participants Who Developed Grade II, Acute GVHD |
— | — |
| SECONDARY Number of Participants Who Developed Grade III, Acute GVHD |
2 | — |
| SECONDARY Number of Participants Who Developed of Grade IV, Acute GVHD |
— | — |
| SECONDARY Number of Participants Who Developed Chronic GVHD |
— | — |
| SECONDARY Number of Participants Who Developed Limited Chronic GVHD |
— | — |
| SECONDARY Number of Participants With Extensive, Chronic GVHD |
— | — |
| SECONDARY Number of Participants With CD3+ Engraftment Who Achieved Peak Chimerism Post DLI |
3 | — |
| SECONDARY Number of Subjects Leukemia Response After Donor Lymphocyte Infusion (DLI) |
— | — |
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. 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.
Eligibility Criteria
- ELIGIBILITY CRITERIA:
Inclusion Criteria- Recipient:
- 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
- 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
Exclusion Criteria Recipient (any of the following):
- 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).
- 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.
Inclusion Criteria- Stem Cell Donors:
- 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.
Exclusion Criteria Stem Cell Donor (any of the following):
- 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.
Inclusion criteria- Haplo Lymphocyte Donors:
- 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 h
Data sourced from ClinicalTrials.gov (NCT00859586). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.