Clinical trial · Interventional
Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases
A Phase II Trial of Total Body Irradiation-Based Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies
- 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)
In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Leukemia | Acute Leukemia | ONTOLOGY_EXACT | 0.90 |
| Chronic Leukemia | Chronic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Hodgkin's Disease | Hodgkin Lymphoma | ALIAS | 0.90 |
| Myelodysplastic Syndrome | Myelodysplastic Syndrome | CURATED_BROADER | 0.80 |
| Non-Hodgkin's Lymphoma | Non-Hodgkin Lymphoma | ALIAS | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Peripheral Blood Stem Cell Transplant | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Myeloablative Haploidentical Transplant
- description
- Haplo transplant
- interventionNames
- Procedure: Peripheral Blood Stem Cell Transplant
Primary outcomes (1)
- measure
- Percentage of Patients Experiencing Hemorrhagic Cystitis Post Transplant
- timeFrame
- 6 months
- description
- 1.1 To estimate the incidence of BK virus-associated hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies.
Secondary outcomes (6)
- measure
- Survival
- timeFrame
- 2 year
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 60 Years
Show eligibility criteria text
Inclusion Criteria: * No available matched related or unrelated donor OR a matched related or unrelated donor that is unavailable in the time frame necessary * Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor * Donor must have a negative HLA cross-match in the host vs. graft direction * Donor must be willing to donate mobilized peripheral blood stem cells * Age 18 to \</=60 years * Karnofsky Status \>/= 70% * Must have one of the following high-risk malignancies * Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to TKI * CML in accelerated phase * CML blast crisis that has entered into 2nd Chronic phase following induction * Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR) * AML primary induction failure but subsequently in CR * AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic disease * AML with marrow blasts \<5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH * Myelodysplastic Syndrome (MDS) that is treatment related * MDS that has monosomy 7 or complex cytogenetics * MDS with IPSS score of 1.5 or greater * Chronic myelomonocytic leukemia (CMML) * Acute Lymphocytic Leukemia/lymphoblastic lymphoma (ALL) in 2nd or subsequent complete remission (CR) * ALL with poor-risk karyotype \[t(9;22) or bcr-abl fusion, t(4;11) or other MLL translocation\] and in 1st CR * ALL with marrow blasts \< 5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH * Chronic Lymphocytic Leukemia (CLL)/Prolymphocytic Leukemia (PLL) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) * Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse) with previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation AND in the opinion of the transplant physician is unlikely to benefit from reduced intensity transplantation due to the presence of one or more high risk features (i.e. bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) * Advance Myelofibrosis, Primary or Post-Polycythemia Vera/Essential Thrombocythemia. Patients must have one of more of the following accelerate phase features, which have been associated with a median overall survival of \</= 15 months * Blood or bone marrow blasts \>/= 10% * Platelets \< 50 x 10\*9/L * Chromosome 17 aberrations Exclusion Criteria: * Patients will not be excluded on the basis of sex, racial or ethnic background * Poor cardiac function: Left ventricular ejection fraction \< 45% * Poor pulmonary function: FEV1 and FVD \< 60% predicted * Poor liver function: bilirubin \>/= 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT \> 3x ULN * Poor renal function: Creatinine \>/= 2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) \< 40 mL/min based on Traditional Cockcroft-Gault formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum creatinine (mg/dl) * HIV positive * Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception * Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up. * Prior irradiation therapy rendering patient ineligible for TBI
References
Publications (14)
- BACKGROUNDSzydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77. doi: 10.1200/JCO.1997.15.5.1767. PMID 9164184
- BACKGROUNDZuckerman T, Rowe JM. Alternative donor transplantation in acute myeloid leukemia: which source and when? Curr Opin Hematol. 2007 Mar;14(2):152-61. doi: 10.1097/MOH.0b013e328017f64d. PMID 17255793
- BACKGROUNDAnasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197-204. doi: 10.1056/NEJM198901263200401. PMID 2643045
- BACKGROUNDAnasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, Thomas ED, Hansen JA. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990 Oct;29(2):79-91. doi: 10.1016/0198-8859(90)90071-v. PMID 2249952
- BACKGROUNDKanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, Karasuno T, Okamoto S, Hirabayashi N, Iwato K, Maruta A, Fujimori Y, Furukawa T, Mineishi S, Matsuo K, Hamajima N, Imamura M. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000). Blood. 2003 Aug 15;102(4):1541-7. doi: 10.1182/blood-2003-02-0430. Epub 2003 Apr 24. PMID 12714500
- BACKGROUNDKernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987 Jun;43(6):842-7.