Clinical trial · Interventional
Mismatched Donor Lymphocyte Infusions for Relapsed Disease Following Allogeneic Stem Cell Transplantation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Miltenyi Magnetic cell sorter for CD3 | Device | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Miltenyi Magnetic cell sorter for CD3
- description
- 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.
- interventionNames
- Device: Miltenyi Magnetic cell sorter for CD3
Primary outcomes (1)
- measure
- Overall Recipient Survival at 6-month Post-relapse of Disease
- timeFrame
- 6 months post-relapse of disease
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 8 Years
- Maximum age
- 75 Years
Show eligibility criteria text
* ELIGIBILITY CRITERIA: Inclusion Criteria- Recipient: 1. 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) 2. Relapsed disease within 6 months of matched sibling allogeneic stem cell transplant procedure 3. Evaluation for protocol within 8 weeks of relapse and enrollment within 12 weeks or relapse 4. 8-75 years of age 5. Availability of previous HLA identical (6/6) related donor (ages 8 to 17 must have previously donated bone marrow \[not peripheral blood\] 6. At least one haploidentical (1-3 antigen mismatched) related donor available for apheresis Exclusion Criteria Recipient (any of the following): 1. Active grade II-IV Graft vs. Host Disease (GvHD) 2. Extensive chronic Graft vs. Host Disease (GvHD) 3. Post-transplant donor lymphocyte infusion (DLI) from original donor within 1 month of protocol enrollment. 4. Progressive disease despite post-relapse chemo or monoclonal therapy. 5. Co-morbidity of such severity that it would preclude the patients ability to tolerate protocol therapy. 6. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 10 x ULN (grade 3, CTCAE). 7. Bilirubin greater than 5 x Upper Limit of Normal (ULN) (grade 3, CTCAE). 8. Creatinine greater than 3.5 mg/dl (grade 3, CTCAE). 9. 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). 10. Positive pregnancy test for women of childbearing age. 11. 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: 1. 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. 2. 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. 3. Weight greater than or equal to 18 kg 4. 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): 1. Pregnant or lactating 2. Unfit to receive filgrastim (G-CSF) or previous filgrastim mobilization for donors under 18 years of age. 3. Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension). 4. Sickling hemoglobinopathies such as HbSS or HbSC. 5. 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. 6. 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: 1. 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. 2. 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): 1. Pregnant or lactating 2. Unfit to undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension). 3. Sickling hemoglobinopathies such as HbSS and HbSC . 4. 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. 5. Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the donation of stem cells unlikely and/or informed consent impossible
References
Publications (3)
- BACKGROUNDArmitage JO. Bone marrow transplantation. N Engl J Med. 1994 Mar 24;330(12):827-38. doi: 10.1056/NEJM199403243301206. No abstract available. PMID 8114836
- BACKGROUNDMontero 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. PMID 17162214
- BACKGROUNDLevine 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. PMID 11786567