Total Marrow and Lymphoid Irradiation Before Donor Transplant and Cyclophosphamide in Treating Patients With Acute Myeloid Leukemia
NCT ID: NCT03467386
Last Updated: 2025-02-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
18 participants
INTERVENTIONAL
2018-03-19
2026-04-06
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia
NCT02446964
Total Marrow and Lymphoid Irradiation and Chemotherapy Before DSCT in Treating Patients With High-Risk ALL or AML
NCT02094794
Total Marrow and Lymphoid Irradiation, Fludarabine, and Melphalan Before Donor Stem Cell Transplant in Treating Participants With High-Risk Acute Leukemia or Myelodysplastic Syndrome
NCT03494569
Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Older Patients With Chronic Myeloid Leukemia
NCT00003145
Total Marrow and Lymphoid Irradiation and Chemotherapy for Myelodysplastic Syndrome or Acute Leukemia
NCT03408210
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To evaluate the safety/feasibility of combining a total marrow and lymphoid irradiation (TMLI) transplant conditioning regimen with a post-transplant high dose cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis strategy, through the assessment of: adverse events: type, frequency, severity, attribution, time course, duration and complications: including acute GvHD, infection and delayed neutrophil/platelet engraftment.
SECONDARY OBJECTIVES:
I. To estimate the cumulative incidence (CI) of acute GvHD at 100 days post allogeneic hematopoietic cell transplantation (alloHCT).
II. To estimate the CI of chronic GvHD at 6 months, 1- and 2-years post alloHCT.
III. To estimate GVHD-free relapse-free survival (GRFS) at 1- and 2-years post alloHCT.
IV. To describe the kinetics of immune reconstitution and T cell repertoire in the first year post alloHCT.
V. To estimate overall survival (OS), relapse-free survival (RFS) and CI of relapse, and non-relapse mortality (NRM) at 100 days, 1- and 2-years post alloHCT.
VI. To characterize quality of life using 36-Item Short Form Health Survey (SF-36), Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and M. D. Anderson Symptom Inventory (MDASI) or Pediatric Quality of Life Inventory (PedsQL) at 100 days, 6 months, 1- and 2-years post alloHCT.
VII. To assess bone marrow cellularity from bone marrow samples. VIII. To assess the clonogenic potential of cells from bone marrow samples. IX. To assess stromal damage from bone marrow samples. X. To evaluate cytokines and oxidative stress markers.
OUTLINE: This is a dose-escalation study of TMLI.
Patients undergo TMLI twice daily (BID) on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide intravenously (IV) over 2 hours on days 3 and 4, tacrolimus given by continuous intravenous infusion (CIV) on days 5-90, and filgrastim beginning on day 5 until absolute neutrophil count (ANC) is at least 1,500/mm\^3 for 3 consecutive days.
After completion of study treatment, patients are followed for up to 24 months.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (TMLI, cyclophosphamide)
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.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo alloHCT
Cyclophosphamide
Given IV
Filgrastim
Administer according to City of Hope standard operating procedures
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Tacrolimus
Given CIV
Total Marrow Irradiation
Undergo TMLI
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo alloHCT
Cyclophosphamide
Given IV
Filgrastim
Administer according to City of Hope standard operating procedures
Laboratory Biomarker Analysis
Correlative studies
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
Tacrolimus
Given CIV
Total Marrow Irradiation
Undergo TMLI
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Karnofsky performance status (KPS) \>= 70%
* The effects of radiation on the developing fetus are known to be teratogenic; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
* Patients with acute myelogenous leukemia (AML) who are in first or second complete remission
* All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate primed blood stem cells (preferred) or bone marrow, or have a 10/10 allele matched unrelated donor; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques; (red cell exchange or plasma exchange)
* A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of \>= 50% established by multi-gated acquisition scan (MUGA) or echocardiogram
* Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance \> 70 ml/min as calculated by the Cockcroft-Gault formula
* A bilirubin of less than or equal to 1.5 mg/dL, excluding patients with Gilbert's disease
* Patients should also have a serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
* Pulmonary function tests including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV 1) and DLCO should be greater than 50% of predicted normal value
* All subjects must have the ability to understand and the willingness to sign a written informed consent; signed informed consent form approved by the Institutional Review Board (IRB) is required; the patient, family member, and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting, all pertinent information with respect to risks and benefits to the donor and recipient will be presented; alternative treatment modalities will be discussed
* The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days
* Prior therapy with etoposide and cyclophosphamide is allowed
* DONOR: donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP)
Exclusion Criteria
* Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; maintenance therapy with Food and Drug Administration (FDA)-approved targeted therapies (e.g. tyrosine kinase inhibitors for Philadelphia chromosome \[Ph\] positive \[+\] acute lymphoblastic leukemia \[ALL\], and FLT inhibitors for FLT3+ patients) will be allowed after day 60 disease assessment
* Prior radiation therapy that would exclude the use of TMLI
* Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously
* Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
* Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction \< 50%
* Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment
* Patients with other active malignancies are ineligible for this study, other than localized malignancies
* Patients that are pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, including but not limited to, infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
* Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
16 Years
60 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
City of Hope Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Anthony S Stein
Role: PRINCIPAL_INVESTIGATOR
City of Hope Comprehensive Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
City of Hope Medical Center
Duarte, California, United States
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2018-00177
Identifier Type: REGISTRY
Identifier Source: secondary_id
17423
Identifier Type: OTHER
Identifier Source: secondary_id
17423
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.