Total Marrow and Lymphoid Irradiation Before Donor Transplant and Cyclophosphamide in Treating Patients With Acute Myeloid Leukemia

February 12, 2026 updated by: City of Hope Medical Center

Pilot Study of Total Marrow/Lymphoid Irradiation (TMLI) Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplant (HCT) Followed by Post Transplant Cyclophosphamide-Based Graft Versus Host Disease Prophylaxis for Acute Myelogenous Leukemia in Complete Remission

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVE:

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • This study is open to patients with acute myeloid leukemia (AML) evaluated within 30 days of the start of conditioning regimen and in first or second complete remission (CR)
  • 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 should not have any uncontrolled illness including ongoing or active or poorly controlled infection
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Radiation: Total Marrow Irradiation
Undergo TMLI
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo alloHCT
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT
  • Stem Cell Transplantation, Allogeneic
Biological: Filgrastim
Administer according to City of Hope standard operating procedures
Other Names:
  • G-CSF
  • r-metHuG-CSF
  • Neupogen
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim
Drug: Tacrolimus
Given CIV
Other Names:
  • Prograf
  • Hecoria
  • FK 506
  • Fujimycin
  • Protopic

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
1a. Incidence of adverse events
Time Frame: Up to 24 months
Assessed using Bearman Scale Regimen-Related Toxicity scale. Scale range: Grade 0-4 (increasing grade reflects increasing severity), where Grade 0-none/did not experience and Grade 4=death.
Up to 24 months
1b. Incidence of adverse events
Time Frame: Up to 24 months
Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. Scale range: Grade 1-5 (increasing grade reflects increasing severity), where Grade 1 reflects a more milder form of the adverse event and Grade 5=death.
Up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to neutrophil and platelet recovery/engraftment
Time Frame: From day 0 to recovery or declaration of engraftment failure, assessed up to 24 months
From day 0 to recovery or declaration of engraftment failure, assessed up to 24 months
Acute graft versus host disease (GvHD)
Time Frame: Day 0 to 100 (120) days post-transplant
Graded according to the Consensus Grading. The first day of acute GvHD onset at a certain grade will be used to calculate cumulative incidence curves for that GvHD grade; relapse/death prior to onset will be considered competing events. Will be calculated using the competing risk method as described by Gooley et al. (1999).
Day 0 to 100 (120) days post-transplant
Chronic GVHD
Time Frame: From day (80) 100 to the onset of chronic GvHD, death or last contact, whichever comes first, assessed up to 24 months
The first day of chronic GvHD onset will be used to calculate cumulative incidence curves, with relapse/death prior to onset considered competing events. Will be calculated using the competing risk method as described by Gooley et al. (1999).
From day (80) 100 to the onset of chronic GvHD, death or last contact, whichever comes first, assessed up to 24 months
GvHD-free/relapse-free survival (GRFS)
Time Frame: From start of treatment (hematopoietic stem cell transplant [HCT]) to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed p to 24 months
Will be calculated using the Kaplan-Meier method.
From start of treatment (hematopoietic stem cell transplant [HCT]) to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed p to 24 months
Levels of immune cells
Time Frame: Up to 24 months
Will be measured by flow cytometry for cell subsets: a. T-cells.
Up to 24 months
Levels of immune cells
Time Frame: Up to 24 months
Will be measured by flow cytometry for cell subsets: b. B-cells.
Up to 24 months
Levels of immune cells
Time Frame: Up to 24 months
Will be measured by flow cytometry for cell subsets: c. natural killer (NK) cells.
Up to 24 months
Levels of immune cells
Time Frame: Up to 24 months
Will be measured by flow cytometry for cell subsets: d. regulatory T cells (T-regs).
Up to 24 months
Overall survival
Time Frame: From start of treatment until death, or last follow-up, whichever comes first, assessed up to 24 months
Will be calculated using the Kaplan-Meier method.
From start of treatment until death, or last follow-up, whichever comes first, assessed up to 24 months
Relapse-free survival
Time Frame: From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 24 months
Will be calculated using the Kaplan-Meier method.
From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 24 months
Relapse
Time Frame: From start of therapy, assessed up to 24 months
Will be calculated using the competing risk method as described by Gooley et al. (1999).
From start of therapy, assessed up to 24 months
Non-relapse mortality (NRM)
Time Frame: From start of treatment until non-disease related death, or last follow-up, whichever comes first, assessed up to 24 months
The cumulative incidence of NRM will be calculated reflecting relapse as a competing risk. Will be calculated using the Kaplan-Meier method and the competing risk method as described by Gooley et al. (1999).
From start of treatment until non-disease related death, or last follow-up, whichever comes first, assessed up to 24 months
Quality of life -Questionnaire
Time Frame: Up to 24 months

Assessed using a. 36-Item Short Form Health Survey (SF-36). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

The eight sections are:

  • a1. vitality
  • a2. physical functioning
  • a3. bodily pain
  • a4. general health perceptions
  • a5. physical role functioning
  • a6. emotional role functioning
  • a7. social role functioning
  • a8. mental health
Up to 24 months
Quality of life-Function Assessment
Time Frame: Up to 24 months

Assessed using b. Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). (FACT-BMT) is a 47-item, valid and reliable measure of five dimensions of quality of life in bone marrow transplant patients. The dimensions collected and assessed are:

  • b1.physical well being
  • b2. Social and family well being
  • b3. Emotional well being
  • b4. Functional well being
  • b5. Additional concerns.
Up to 24 months
Quality of life -Symptom Inventory
Time Frame: Up to 24 months

Assessed using c. M. D. Anderson Symptom Inventory (MDASI). MDASI is a multi-symptom patient-reported outcome (PRO) measure for clinical and research use. Use the MDASI to assess the severity of symptoms experienced by patients with cancer and the interference with daily living caused by these symptoms. The following parameters will be reported:

  • c1a. Pain
  • c1b. Fatigue
  • c1c. Nausea
  • c1d. Disturbed sleep
  • c1e. Distress/feeling upset
  • c1f. Shortness of breath
  • c1g. Difficulty remembering
  • c1h. Lack of appetite
  • c1i. Drowsiness
  • c1j. Dry mouth
  • c1k. Sadness
  • c1l. Vomiting
  • c1m. Numbness/tingling
  • c1n. Walking
  • c1o. Activity
  • c1p. Working (including housework)
  • c1q. Relations with other people
  • c1r. Enjoyment of life
  • c1s. Mood A total of eight quality of life parameters will be reported on each pediatric transplant patient.
  • c2a.Pain and Hurt
  • c2b. Fatigue and Sleep
  • c2c. Nausea
  • c2d. Worry
  • c2e. Nutrition
  • c2f. Thinking
  • c2g. Communication
Up to 24 months
Bone marrow residual damage assessment
Time Frame: Up to 24 months
Up to 24 months
Cytokines
Time Frame: Up to 24 months
Up to 24 months
Oxidative stress Markers
Time Frame: Up to 24 months
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
City of Hope Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anthony S Stein, City of Hope Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 19, 2018

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 6, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 6, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17423 (Other Identifier: City of Hope Comprehensive Cancer Center)
  • NCI-2018-00177 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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