Stem Cell Transplant for Blood Cancers
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
Must not be taking: Alemtuzumab, ATG
Disqualifiers: HIV, CNS malignancy, Psychiatric disorder, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial studies the how well donor stem cell transplant works in treating patients with high risk hematologic malignancies. Giving total-body irradiation and chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and total-body irradiation, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.
What data supports the effectiveness of the treatment Allogeneic Hematopoietic Stem Cell Transplantation for blood cancers?
Research shows that using total body irradiation (TBI) combined with cyclophosphamide (a chemotherapy drug) as part of the pre-transplant preparation can improve survival outcomes in patients with acute lymphoblastic leukemia (ALL), a type of blood cancer. This combination is a common and effective approach in preparing patients for stem cell transplants.
12345Is stem cell transplant for blood cancers generally safe for humans?
Stem cell transplants, including those using donor cells, have been studied for safety. While they can be effective, they come with risks like graft-versus-host disease (GVHD), where the donor cells attack the recipient's body. However, using medications like cyclophosphamide and tacrolimus can help reduce these risks, and recent studies show improved safety outcomes with these treatments.
16789How is the treatment of allogeneic hematopoietic stem cell transplantation with cyclophosphamide and total-body irradiation unique for blood cancers?
This treatment is unique because it combines donor stem cell transplantation with a conditioning regimen of cyclophosphamide (a chemotherapy drug) and total-body irradiation (TBI), which helps prepare the body to accept new stem cells by suppressing the immune system and eliminating cancer cells. The use of TBI and cyclophosphamide is a well-established approach for treating acute and chronic leukemias, and it aims to reduce the risk of graft-versus-host disease (a condition where the donor cells attack the recipient's body) while enhancing the effectiveness of the transplant.
25101112Eligibility Criteria
This trial is for adults with high-risk blood cancers who have a partially matched related donor. They must be in good health with proper heart, lung, liver function, and kidney clearance. A performance status showing they're mostly independent in daily activities is required. HIV-positive individuals, those with central nervous system cancer involvement or significant psychiatric disorders are excluded.Inclusion Criteria
I have a rare condition that could benefit from a stem cell transplant.
Patients must be willing to use contraception if they have childbearing potential
My heart, lungs, liver, kidneys, and overall health are in good condition.
+5 more
Exclusion Criteria
I am HIV positive.
I cannot tolerate certain doses of cyclophosphamide or total body irradiation.
> 5 Comorbidity Points on the Hematopoietic Cell Transplant Co-Morbidity Index (HCT CI)
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Radiation
Participants undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8
1 week
Daily visits for radiation
Chemotherapy and Transplantation
Participants receive chemotherapy and undergo Allogeneic Hematopoietic Stem Cell Transplantation
4 weeks
Inpatient stay for chemotherapy and transplantation
Follow-up
Participants are monitored for safety, effectiveness, and immune recovery after treatment
2 years
Participant Groups
The study tests if a stem cell transplant from a donor after receiving full-body radiation and chemotherapy can treat patients with aggressive blood cancers effectively without causing severe side effects. The goal is to stop cancer growth and prevent the immune system from rejecting the new cells.
1Treatment groups
Experimental Treatment
Group I: Treatment (TBI, DLI, chemotherapy, HSCT)Experimental Treatment6 Interventions
Patients undergo Total-Body Irradiation (TBI) twice daily on days -10 to -8 and and donor lymphocyte infusion (DLI) on day -6. Patients receive cyclophosphamide IV on days -3 and -2, tacrolimus IV beginning on day -1 and then orally at least 2 or 3 days prior to discharge with taper starting on day 42, and mycophenolate mofetil IV twice daily on days -1 to 28. Patients undergo Allogeneic Hematopoietic Stem Cell Transplantation on day 0.
Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:
- Primary immunodeficiency disorders
- Immune dysregulatory disorders
- Hemophagocytic lymphohistiocytosis
- Bone marrow failure syndromes
- Hemoglobinopathies
🇺🇸 Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:
- Primary immunodeficiency disorders
- Immune dysregulatory disorders
- Hemophagocytic lymphohistiocytosis
- Bone marrow failure syndromes
- Hemoglobinopathies
🇨🇦 Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:
- Primary immunodeficiency disorders
- Immune dysregulatory disorders
- Hemophagocytic lymphohistiocytosis
- Bone marrow failure syndromes
- Hemoglobinopathies
🇯🇵 Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:
- Primary immunodeficiency disorders
- Immune dysregulatory disorders
- Hemophagocytic lymphohistiocytosis
- Bone marrow failure syndromes
- Hemoglobinopathies
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, PA
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Who Is Running the Clinical Trial?
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityLead Sponsor
References
Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. [2023]To observe the therapeutic effect and the incidence of adverse reactions of total body irradiation plus cyclophosphamide (TBI/CY) and busulfan plus cyclophosphamide (BU/CY) in the treatment of pediatric hematopoietic stem cell transplantation.
Twenty years of experience of a tertiary cancer center in total body irradiation with focus on oncological outcome and secondary malignancies. [2022]Total body irradiation (TBI) is a common part of the myelo- and immuno-ablative conditioning regimen prior to an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to concerns regarding acute and long-term complications, there is currently a decline in otherwise successfully established TBI-based conditioning regimens. Here we present an analysis of patient and treatment data with focus on survival and long-term toxicity.
Acute Lymphoblastic Leukemia in Children: Better Transplant Outcomes After Total Body Irradiation-based Conditioning. [2021]Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT).
Irradiation free conditioning regimen is associated with high relapse rate in Egyptian patients with acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation. [2021]Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for adult patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide plus total body irradiation (TBI/Cy) or plus busulfan (Bu/Cy) is a widely used pre-transplant conditioning regimen for ALL. We retrospectively compared the overall survival (OS), disease-free survival (DFS), and other transplant outcomes of allo-HSCT in 119 adult patients with ALL who received an HLA-matched sibling allo-HSCT using TBI-based versus non-TBI-based conditioning regimens. Patients were divided into two groups by their conditioning regimen: TBI/Cy or Bu/Cy.
Effect of the duration between total body irradiation and stem cell infusion on the outcome of allogeneic transplantation with myeloablative conditioning. [2015]Limited data are available on the effect of how cyclophosphamide (CY) and total body irradiation (TBI) are administered. We analyzed the effect of the interval from TBI to hematopoietic stem cell transplantation (HSCT) on the outcome of HSCT.
Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors. [2018]Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571.
Current Use of Total Body Irradiation in Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation. [2021]Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT.
Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. [2021]Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative therapy for many hematologic and immunologic diseases. Further, partial or full donor hematopoietic chimerism following alloSCT may be sufficient to guarantee immunologic tolerance to solid organs from the same donor, obviating any requirement for prolonged pharmacologic immunosuppression. Despite alloSCT's potential, the procedure is beset by two major limitations. The first relates to the procedure's toxicity, including conditioning regimen toxicity, graft-versus-host disease (GVHD), and infection. The second limitation is the lack of histocompatible donors. A human leukocyte antigen (HLA)-matched sibling or unrelated donor cannot be identified expeditiously for up to 40% of patients. Historically, alloSCT from partially HLA-mismatched, or HLA-haploidentical, relatives has been complicated by unacceptably high incidences of graft rejection, severe GVHD, and non-relapse mortality. Recently, our groups have developed a method to selectively deplete alloreactive cells in vivo by administering high doses of cyclophosphamide in a narrow window after transplantation. Using high-dose, post-transplantation cyclophosphamide (PT/Cy), crossing the HLA barrier in alloSCT is now feasible and donors can be found for nearly all patients. This review discusses the history of HLA-haploidentical SCT, recent clinical results, and immunologic mechanisms of action of high-dose PT/Cy for prevention of graft rejection and GVHD.
[Nonmyeloablative allogeneic hematopoietic stem cell transplantation: minitransplantation]. [2006]Allogeneic hematopoietic stem cell transplantation (alloHCT) is considered as a treatment of choice for many malignant hematologic disorders and genetic diseases. Unfortunately toxicities of conventional alloHCT remain a major limitation to successful application of the procedure. A radically new approach for alloHCT has been developed. Nonmyeloablative preparative regimen allows to establish mixed hematopoietic chimerism after alloHCT. A state of stable mixed chimerism may represent a starting point for induction of full donor derived hematopoiesis. A published results of several clinical trials have confirmed potential benefits of this new approach such as less procedure--related toxicity, protection from severe acute GVHD (graft versus host disease), lower TRM (transplant related mortality). Intensive investigations are done to replace in the future pretransplant chemotherapy and/or radiation by nontoxic anti-T-cell agents. These include antibody to the T-cell receptor alpha beta and blockers of T-cell costimulation (e.g. CTLA4lg).
Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies. [2017]To determine the efficacy and toxicity of etoposide, cyclophosphamide, and fractionated total-body irradiation (TBI) as the conditioning regimen for allogeneic bone marrow transplantation (BMT) in patients with hematologic malignancies.
[Bone marrow transplantation with T-cell depletion and hyperfractionated whole-body irradiation. The radiobiological and clinical correlations]. [2008]Total body irradiation (TBI) and cyclophosphamide (Cy) is the conventional conditioning regimen for the patients who are to receive bone marrow transplantation (BMT). It is one of the most effective treatments for acute and chronic leukemias. In this paper we discuss the clinical and radiobiological features relative to TBI methods and to the kind of BMT. Graft-versus-host disease (GvHD) incidence is decreased by the depletion of T-lymphocytes from donor's bone marrow which causes high rates of rejection and relapses. Thus, more aggressive conditioning regimens are necessary than unmanipulated BMT. The results are also examined of different experimental and clinical trials on the immunohematological features of T-depleted BMT and the radiobiological behavior of normal and pathological target tissues due to different methods of TBI. We report the experience of the Perugia Bone Marrow Transplantation Unit and Radiation Oncology Service. We treated 54 patients suffering from acute leukemia (AL) and 34 cases with chronic myeloid leukemia (CML) with T-depleted allogeneic HLA-identical BMT. Three different conditioning regimens were employed in an effort to enhance cytoreduction and immunosuppression without significantly increasing extramedullary toxicity. TBI was administered according to a hyperfractionated scheme of 3 fractions a day for 4 days. The third conditioning regimen, including also thiothepa (TT), gave the best results in terms of stable uptake and leukemic cells eradication. Disease-free survival (DFS) is 55.5% in the patients with AL at a median follow-up of 40 months; in the patients with CML who were not treated with TT, DFS is 10% at a median follow-up of 60 months, while it is 66.6% at a median follow-up of 12 for the group of patients who received also TT. The conditioning regimen with hyperfractionated TBI, Cy and TT was effective and well tolerated; 12.5% of patients developed interstitial pneumonia.
[Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy]. [2014]To investigate the therapeutic effects of the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) or total body irradiation plus cyclophosphamide (TBI+CY) on haploidentical stem cell transplantation (HSCT) in hematologic malignancy.