Bone Marrow Irradiation + Cyclophosphamide for Acute Myeloid Leukemia
Recruiting in Palo Alto (17 mi)
Overseen byAnthony S Stein
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: City of Hope Medical Center
Must not be taking: Investigational agents
Disqualifiers: Uncontrolled illness, Prior transplant, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
This pilot phase I trial studies the side effects of total bone marrow and lymphoid irradiation and how well it works with cyclophosphamide in treating patients with acute myeloid leukemia. Total marrow and lymphoid irradiation targets cancer in bone marrow and blood, instead of applying radiation to the whole body. Giving total bone marrow and lymphoid irradiation before a donor transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving total bone marrow and lymphoid irradiation before donor transplant and cyclophosphamide after transplant may work better at treating acute myeloid leukemia.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or concurrent biological, chemotherapy, or radiation therapy. Maintenance therapy with certain FDA-approved targeted therapies is allowed after day 60.
What data supports the effectiveness of the treatment Bone Marrow Irradiation + Cyclophosphamide for Acute Myeloid Leukemia?
Research shows that using cyclophosphamide with total body irradiation (TBI) as part of a treatment plan for leukemia can be effective, with a 5-year survival rate of 54% and a low relapse rate of 7% in one study. This suggests that the combination of these therapies can help control the disease and improve survival outcomes.12345
Is the combination of bone marrow irradiation and cyclophosphamide generally safe for humans?
The combination of bone marrow irradiation and cyclophosphamide has been studied in various settings, including for leukemia treatment. While it can be effective, there are risks of severe side effects, such as cardiac (heart) toxicity and gastrointestinal issues. However, many patients have successfully undergone treatment with careful monitoring and supportive care.14678
How does the treatment of Bone Marrow Irradiation + Cyclophosphamide for Acute Myeloid Leukemia differ from other treatments?
This treatment is unique because it combines bone marrow irradiation with cyclophosphamide, focusing the radiation specifically on the bone marrow rather than the whole body, which may reduce side effects compared to total body irradiation. This approach aims to effectively target leukemia cells while potentially minimizing damage to other tissues.12469
Eligibility Criteria
This trial is for adults with acute myeloid leukemia in first or second complete remission. Participants must have a matched sibling or unrelated donor for stem cell transplant, good heart and kidney function, and no recent chemotherapy or radiation. They should not be pregnant, agree to use contraception, and be able to give informed consent.Inclusion Criteria
My AML is in the first or second complete remission.
It has been at least 14 days since my last cancer treatment session.
Pulmonary function tests including DLCO and FEV 1 greater than 50% of predicted normal value
See 11 more
Exclusion Criteria
I am not currently on any experimental treatments or undergoing chemotherapy or radiation.
I have a health or mental condition that makes stem cell transplant unsafe for me.
Abnormal EKG, echocardiogram, or MUGA scan results
See 8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Radiation
Patients undergo total marrow and lymphoid irradiation (TMLI) twice daily on days -4 to 0
1 week
Daily visits for radiation
Transplantation
Patients undergo bone marrow or peripheral blood stem cell transplant on day 0
1 day
1 visit (in-person)
Chemotherapy
Patients receive cyclophosphamide intravenously over 2 hours on days 3 and 4
2 days
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of GvHD and quality of life
24 months
Regular follow-up visits
Treatment Details
Interventions
- Cyclophosphamide (Alkylating agents)
- Total Marrow Irradiation (Radiation Therapy)
Trial OverviewThe trial tests total marrow and lymphoid irradiation followed by a stem cell transplant from a donor, along with cyclophosphamide treatment. It aims to see how well this approach works compared to traditional whole-body radiation therapy in treating leukemia without harming other organs.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (TMLI, cyclophosphamide)Experimental Treatment8 Interventions
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm\^3 for 3 consecutive days.
Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Cytoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Neosar for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
- Rheumatoid arthritis
🇯🇵 Approved in Japan as Endoxan for:
- Breast cancer
- Ovarian cancer
- Multiple myeloma
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia. [2013]This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.
Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis. [2018]Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen.
Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen--a report from the acute leukemia working party of the European group for blood and marrow transplantation. [2022]Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a safer toxicity profile than the oral formulation. Comparative studies of outcomes have been performed between oral Bu/Cy and Cy/TBI, but there have been no comparative trials in the era of IV Bu.
Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide. [2013]Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell rescue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens consisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI). Subsequent attempts have been made to improve leukemia-free survival, by adding other chemotherapy agents to these agents. In previous clinical studies of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incidence of severe regimen-related toxicity. In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12-14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg x 2) and then either matched sibling or alternative donor transplants for acute leukemia. There was only one case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53-88%). The estimated event-free survival of patients with advanced disease was 17% (5-59%). TBI-VP16-CY is safe in pediatric transplantation, and it has good efficacy for transplant recipients with less advanced disease. Bone Marrow Transplantation (2000) 25, 489-494.
Busulfan, cyclophosphamide and total body irradiation as conditioning for allogeneic bone marrow transplantation for acute and chronic myeloid leukemia. [2013]Fifty patients with acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) underwent allogeneic bone marrow transplantation between October 1988 and January 1997. Patients received 8 mg/kg of busulfan (BU) with 120 mg/kg of cyclophosphamide (CY) followed by 10 Gy of total body irradiation (TBI). Twenty consecutive patients with AML in first remission (n = 9) or CML, in chronic phase (n = 11) entered the study (group I). Thirty consecutive patients with advanced myeloid malignancies including AML (n = 19) and CML (n = 11) also entered the study (group II). The probability of leukemia-free survival at 5 years was 85% for group I patients and 50% for group II patients. Severe regimen-related toxicities occurred in 16% of patients (two in group I, six in group II). The most common sites affected by severe toxicities were lung (n = 6), liver (n = 2) and heart (n = 2). The relapse rate was higher for patients allografted in advanced stages of disease (O% at 5 years for group I and 28% for group II). These results suggest that BU + CY + TBI is a very effective conditioning regimen in patients with myeloid malignancies.
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.
High-dose therapy and bone marrow transplantation. [2018]Toxicity to the bone marrow is a frequent limiting factor in the use of high doses of chemotherapeutic agents. Bone marrow transplantation overcomes the marrow toxicity problem, but it is not protective to other organs. Extensive animal studies have been carried out in the mouse, the rat, rhesus monkeys, and dogs to delineate the dose-limiting toxicity of cyclophosphamide (Cytoxan) (CY) therapy. Studies in the dog have shown 100 mg/kg of CY to be lethal with supportive care alone. Dogs given this dose followed by stored autologous marrow recovered after a period of profound pancytopenia and severe gastrointestinal toxicity. This dose of CY also permitted allogeneic engraftment in the dog. Monkeys given up to 200 mg/kg of CY have uneventful hematopoietic recovery, but doses of 240 mg/kg were generally fatal even when stored autologous marrow was infused. Cardiac toxicity was the limiting factor. CY 180 mg/kg was not lethal and permitted successful allogeneic marrow engraftment. CY is successfully used for conditioning leukemia or aplastic anemia patients for bone marrow transplantation. Patients with severe aplastic anemia are conditioned with CY 50 mg/kg on each of four days followed by allogeneic marrow transplantation. Patients undergoing transplantation before transfusion have a long-term survival rate of about 80%. Patients with genetic disorders of the marrow generally have a normocellular or hypercellular marrow, and the preparative regimen must include destruction of the abnormal marrow as well as immunosuppression sufficient to permit engraftment. Patients with thalassemia are treated with dimethylbusulfan 5 mg/kg or busulfan 14 mg/kg followed by CY 50 mg/kg on each of four days. Approximately 100 thalassemia patients have been treated, with a survival rate of approximately 75%. For patients with leukemia, radiotherapy is generally added to the CY conditioning regimen. In the early Seattle studies, 1,000 rad total body irradiation was combined with CY 60 mg/kg on each of two days. There were many early deaths, but some long-term survivors are alive and well 5 to 13 years later. Current regimens involve fractionated total body irradiation and various post-grafting immunosuppressive regimens designed to prevent graft-v-host disease. Complications and problems of current regimens are discussed, and future goals for marrow transplantation are presented.
Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide. [2019]Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI).
[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.