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Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 2NCT02094794

Total Marrow and Lymphoid Irradiation and Chemotherapy Before DSCT in Treating Patients With High-Risk ALL or AML

A Phase 2 study testing etoposide, cyclophosphamide and total marrow irradiation in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Del(5q), 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
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Trial summary

This phase II trial studies the safety and efficacy of total marrow and lymphoid irradiation (TMLI) in combination with two chemotherapy drugs, etoposide and cyclophosphamide, as a preparative regimen before donor stem cell transplant in treating patients with high-risk acute lymphocytic leukemia (ALL) or acute… Read more about this study

Who is it for?
Ages 16 to 60 years
What is being tested?
etoposide, cyclophosphamide and total marrow irradiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
1 siteUnited States
Study dates
12 May 2014to 4 May 2027
Phase
Phase 2
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

  • Participant has the ability and the willingness to sign the informed consent document (for adults only, for participants with mild cognitive abilities may use a legally authorized representative)
  • Documented (signed) informed consent; 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 donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent forms
  • Karnofsky performance status >= 70% =< 2
  • Acute lymphocytic leukemia or acute myelogenous leukemia who are not in first remission or second remission i.e. after failing induction therapy, or in relapse or beyond second remission; (prior therapy with VP-16 and Cytoxan is allowed)
  • All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate bone marrow or primed blood stem cells or a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR or DQ and a killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable
  • The time from the end last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days from planned start of study treatment; Note: Chemotherapy given within 14 days of planned study enrollment for the purpose of controlling counts is permitted
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  • Total bilirubin =< 1.5 x upper limit of normal (ULN) OR 3 x ULN for Gilbert's disease
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x ULN
  • Measured creatinine clearance >= 80 ml/min per 24 hour urine collection OR serum creatinine =< 1.3 mg/dL
  • Women of child bearing potential only: Negative urine or serum pregnancy test
  • Pulmonary function tests: Forced expiratory volume in one second (FEV1) and carbon monoxide diffusion capacity (DLCO) (adjusted for Hb) >= 50% adjusted of predicted normal value
  • Echocardiogram (ECHO) or multi gated acquisition scan (MUGA): ejection fraction of >= 50% AND no finding of abnormal wall motion (i.e. report does not indicate that wall motion is "abnormal" or "altered")
  • Electrocardiogram (EKG) showing no ischemic changes and no abnormal rhythm
  • Agreement of men AND women-of-child-bearing-potential 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
  • DONOR ELIGIBILITY: Donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP)

Who cannot join

  • Prior autologous or allogeneic hematopoietic stem cell
  • Prior radiation therapy that would exclude the use of TMLI
  • Plans during the trial to receive any other (non-trial) investigational agents, or concurrent biological, chemotherapy, or radiation therapy; (chemotherapy for white blood count control is permitted)
  • Uncontrolled illness including ongoing or active infection
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to etoposide
  • Patients with other active malignancies are ineligible for this study, other than localized malignancies
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  • Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
  • Women who are planning to become pregnant or breast feed during the trial
  • 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: Phase II Study of Total Marrow and Lymphoid Irradiation (TMLI) Given in Combination With Cyclophosphamide and Etoposide as Conditioning for Allogeneic (HSCT) in Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

This phase II trial studies the safety and efficacy of total marrow and lymphoid irradiation (TMLI) in combination with two chemotherapy drugs, etoposide and cyclophosphamide, as a preparative regimen before donor stem cell transplant in treating patients with high-risk acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) who have failed previous therapy. Intensity-modulated radiation therapy (IMRT) uses imaging to provide a three-dimensional view of the area to be irradiated. Doctors can then shape and direct the radiation beams at the area from multiple directions while avoiding, as much as possible, nearby organs. TMLI is a method of using IMRT to direct radiation to the bone marrow. Radiation therapy is given before transplant to suppress the immune system, prevent rejection of the transplanted cells, and wipe out any remaining cancer cells. TMLI may allow a greater radiation dose to be delivered to the bone marrow as a preparative regimen before transplant while causing fewer side effects than standard radiation therapy.

Read the detailed description

PRIMARY OBJECTIVES: I. Following a patient safety lead-in, evaluate the anti-tumor activity of the allogeneic hematopoietic cell transplant (alloHCT) preparative regimen - TMLI, cyclophosphamide (Cy) and etoposide (VP-16), as assessed by 2-year progression-free survival (PFS).

SECONDARY OBJECTIVES: I. Estimate overall survival (OS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

II. Evaluate early and late toxicities/complications by organ and severity, and characterize by organ dose/dose volume, including acute/chronic graft-versus-host-disease (GVHD), infection, and longer-term complications (via protocol #s 07173 and 00029).

OUTLINE: Patients undergo image guided TMLI on days -9 to -5, receive etoposide intravenously (IV) on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.

After completion of study treatment, patients are followed up for 5 years.

Being tested
etoposide, cyclophosphamide, total marrow irradiation, allogeneic hematopoietic stem cell transplantation, allogeneic bone marrow transplantation
Medical subject headings
Congenital Abnormalities, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute

What participants receive

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

  • etoposideDrug

    Also called EPEG, VP-16, VP-16-213

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • total marrow irradiationRadiation

    Undergo TMLI

  • allogeneic hematopoietic stem cell transplantationProcedure or surgery

    Undergo allogeneic peripheral blood stem cell or bone marrow transplant

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Undergo allogeneic peripheral blood stem cell or bone marrow transplant

Study groups in NCT02094794
Study groupRoleWhat they receive
Treatment (TMLI, chemotherapy)ExperimentalPatients undergo image guided TMLI on days -9 to -5, receive etoposide IV on day -4 and cyclophosphamide IV on day -2, and undergo allogeneic peripheral blood stem cell or bone marrow transplant on day 0.
Receives: Drug: etoposide; Drug: cyclophosphamide; Radiation: total marrow irradiation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: allogeneic bone marrow transplantation

What is being measured

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

  1. Incidence of toxicity, scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria version 4.03 (Safety lead-in segment)

    Toxicity information recorded will include the type, severity, and the probable association with the study regimen.

    Measured: Up to 30 days after stem cell infusion

  2. PFS

    Calculated using the Kaplan-Meier method. The cumulative incidence of relapse/progression will be calculated as a competing risk using the Gray method.

    Measured: The time from start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years

Secondary outcomes (9)

  1. OS

    Calculated using the Kaplan-Meier method.

    Measured: The time from start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 5 years

  2. Time to relapse/progression

    Calculated using the Kaplan-Meier method.

    Measured: From start of therapy to time of relapse/progression, assessed up to 5 years

  3. Complete response (CR) proportion

    Measured: The start of therapy to the time of CR, assessed at day 30

  4. NRM

    Calculated using the Kaplan-Meier method. The cumulative incidence of non-relapse mortality will be calculated as a competing risk using the Gray method.

    Measured: From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 5 years

  5. Incidence of infection

    Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: Up to 100 days post-transplant

  6. Incidence of toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

    The worst grade of all toxicities will be collected from day -9 to day -1 and again from day 0 to day 30 post-transplant. From day 31 to 100 post-transplant only grade 3, 4 and 5 toxicities will be collected. Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.

    Measured: Up to day 100 post-transplant

  7. Incidence of acute graft versus host disease GVHD (aGVHD) of grades 2-4, 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.

    Measured: Up to day 100 post-transplant

  8. Incidence of aGVHD of grades 3-4, 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.

    Measured: Up to day 100 post-transplant

  9. Incidence of chronic GVHD, scored according to National Institute of Health Consensus staging

    Measured: Up to 5 years

Timeline

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

  1. First posted24 Mar 2014 (estimated)
  2. Study start12 May 2014
  3. Primary completion4 May 2027 (estimated)
  4. Study completion4 May 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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
108 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02094794
Sponsor's protocol ID
14012
Other IDs
NCI-2014-00639, 14012, R01CA154491
Status last verified
Jun 2026
First submitted
20 Mar 2014
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Stein A, Wang Y, Malki MMA, Aldoss I, Ali H, Aribi A, Artz A, Ball B, Dandapani S, Farol L, Han C, Liu A, Pullarkat V, Radany E, Sahebi F, Sanchez JF, Sandhu K, Salhotra A, Smith E, Spielberger R, Hui S, Marcucci G, Nakamura R, Forman SJ, Palmer J, Wong J. Total marrow and lymphoid irradiation in combination with cyclophosphamide and etoposide before haematopoietic cell transplantation for relapsed or refractory acute leukaemia: a single-centre, open-label, phase 2 trial. Lancet Haematol. 2026 Jun;13(6):e365-e375. doi: 10.1016/S2352-3026(26)00014-1. Epub 2026 May 18.

    PubMed 42150590

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing etoposide, cyclophosphamide and total marrow irradiation in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Del(5q), 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 15 inclusion and 9 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 1 Jul 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Incidence of toxicity, scored on both the Bearman Scale and National Cancer Institute Common Terminology Criteria version 4.03 (Safety lead-in segment) (time frame: Up to 30 days after stem cell infusion). 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 NCT02094794, which also lists 1 linked publication.

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 1 Jul 2026.

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