AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 1NCT03467386

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

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Filgrastim in people with Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 16 to 60 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Filgrastim
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteUnited States
Study dates
19 Mar 2018to 12 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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)

Who cannot join

  • 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%
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Filgrastim, Laboratory Biomarker Analysis, Quality-of-Life Assessment
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo alloHCT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FilgrastimBiological

    Also called G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor

    Administer according to City of Hope standard operating procedures

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given CIV

  • Total Marrow IrradiationRadiation

    Undergo TMLI

Study groups in NCT03467386
Study groupRoleWhat they receive
Treatment (TMLI, cyclophosphamide)ExperimentalPatients 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.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Tacrolimus; Radiation: Total Marrow Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1a. Incidence of adverse events

    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.

    Measured: Up to 24 months

  2. 1b. Incidence of adverse events

    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.

    Measured: Up to 24 months

Secondary outcomes (18)

  1. Time to neutrophil and platelet recovery/engraftment

    Measured: From day 0 to recovery or declaration of engraftment failure, assessed up to 24 months

  2. Acute graft versus host disease (GvHD)

    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).

    Measured: Day 0 to 100 (120) days post-transplant

  3. Chronic GVHD

    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).

    Measured: From day (80) 100 to the onset of chronic GvHD, death or last contact, whichever comes first, assessed up to 24 months

  4. GvHD-free/relapse-free survival (GRFS)

    Will be calculated using the Kaplan-Meier method.

    Measured: 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

  5. Levels of immune cells

    Will be measured by flow cytometry for cell subsets: a. T-cells.

    Measured: Up to 24 months

  6. Levels of immune cells

    Will be measured by flow cytometry for cell subsets: b. B-cells.

    Measured: Up to 24 months

  7. Levels of immune cells

    Will be measured by flow cytometry for cell subsets: c. natural killer (NK) cells.

    Measured: Up to 24 months

  8. Levels of immune cells

    Will be measured by flow cytometry for cell subsets: d. regulatory T cells (T-regs).

    Measured: Up to 24 months

  9. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From start of treatment until death, or last follow-up, whichever comes first, assessed up to 24 months

  10. Relapse-free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 24 months

  11. Relapse

    Will be calculated using the competing risk method as described by Gooley et al. (1999).

    Measured: From start of therapy, assessed up to 24 months

  12. Non-relapse mortality (NRM)

    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).

    Measured: From start of treatment until non-disease related death, or last follow-up, whichever comes first, assessed up to 24 months

  13. Quality of life -Questionnaire

    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

    Measured: Up to 24 months

  14. Quality of life-Function Assessment

    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.

    Measured: Up to 24 months

  15. Quality of life -Symptom Inventory

    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

    Measured: Up to 24 months

  16. Bone marrow residual damage assessment

    Measured: Up to 24 months

  17. Cytokines

    Measured: Up to 24 months

  18. Oxidative stress Markers

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2018
  2. Study start19 Mar 2018
  3. Primary completion12 Apr 2027 (estimated)
  4. Study completion12 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03467386
Sponsor's protocol ID
17423
Other IDs
NCI-2018-00177, 17423
Status last verified
Sep 2026
First submitted
22 Feb 2018
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Filgrastim in people with Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1a. Incidence of adverse events (time frame: Up to 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03467386.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in