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AzTrials

Previously Treated Myelodysplastic SyndromePhase 1NCT02333162

Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

A Phase 1 study testing Fludarabine Phosphate, Melphalan and Intensity-Modulated Radiation Therapy in people with Previously Treated Myelodysplastic Syndrome and Recurrent Adult Acute Lymphoblastic Leukemia, run by University of Chicago at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

This phase I trial studies the side effects and the best dose of intensity modulated total marrow irradiation (IMTMI) when given together with fludarabine phosphate and melphalan in treating patients with cancers of the blood (hematologic) that have returned after a period of improvement (relapsed) undergoing a second… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Fludarabine Phosphate, Melphalan and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
5 Dec 2014to 1 Dec 2028
Phase
Phase 1
Are there results?
None posted in the registry

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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators
  • Karnofsky performance status of 70 or above
  • Life expectancy is not severely limited by concomitant illness
  • Adequate cardiac and pulmonary function; patients with decreased left ventricular ejection fraction (LVEF) =< 40% or diffusion capacity of carbon monoxide (DLCO) =< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol
  • Serum creatinine =<1.5 mg/dL or creatinine clearance > 50 ml/min; some patients with minor deviations may be accepted on protocol after discussion with the principal investigator (PI)
  • Serum bilirubin =< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI
Show all 16Show fewer
  • Serum glutamic oxaloacetic transaminase (SGPT) < 5 x upper limit of normal; some patients with minor deviations may be accepted on protocol after discussion with the PI
  • No evidence of chronic active hepatitis or cirrhosis
  • Human immunodeficiency virus (HIV)-negative
  • Patient is not pregnant
  • Patient or guardian able to sign informed consent
  • DONOR: Since these patients already had first allo-SCT; in the majority time, the same matched donor has been used for second allo-SCT; if the patients have multiple donors, alternative matched (8/8 or 10/10) donor could be used for the second allo-SCT; the donor could be matched related donors or matched unrelated donors from registry
  • DONOR: If more than one potential volunteer unrelated donor is considered suitable, further selection of the most suitable donor will be prioritized as follows or will follow our institutional guideline from our stem cell transplant standard operating procedure (SOP):
  • Age of donor (18-24 > 25-34 > 35-44 > 45+)
  • Sex of donor (male > female, nulliparous female > parous, multiparous female)
  • Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- > CMV+

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: A Phase I Study of Intensity Modulated Total Marrow Irradiation (IMTMI) in Addition to Fludarabine/Melphalan Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

This phase I trial studies the side effects and the best dose of intensity modulated total marrow irradiation (IMTMI) when given together with fludarabine phosphate and melphalan in treating patients with cancers of the blood (hematologic) that have returned after a period of improvement (relapsed) undergoing a second donor stem cell transplant. IMTMI is a type of radiation therapy to the bone marrow that may be less toxic and may also reduce the chances of cancer to return. Giving fludarabine phosphate, melphalan, and IMTMI before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Read the detailed description

PRIMARY OBJECTIVES:

  1. The determine the maximum tolerated dose (MTD) of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine (fludarabine phosphate)/melphalan as conditioning for second allogeneic stem cell transplantation for patients with hematologic malignancies.

SECONDARY OBJECTIVES:

  1. To determine the overall toxicity and day 100 transplant related mortality after second allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan.

II. To determine the time to neutrophil and platelet engraftment after second allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan.

III. To determine the overall survival (OS) and event-free-survival (EFS) in patients with hematologic undergoing second allogeneic hematopoietic stem cell transplant (HSCT) after conditioning with fludarabine/melphalan and IMTMI.

OUTLINE: This is a dose-escalation study of IMTMI.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI twice daily (BID) for 2 to 5 days between days -7 to -3.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) or bone marrow transplant (BMT) on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO) BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60.

After completion of treatment, patients are followed up periodically for 1 year and then yearly for 2 years.

Being tested
Fludarabine Phosphate, Melphalan, Intensity-Modulated Radiation Therapy, Total Marrow Irradiation, Allogeneic Hematopoietic Stem Cell Transplantation
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Hematologic Neoplasms

What participants receive

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

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, Beneflur, SH T 586

    Given IV

  • MelphalanDrug

    Also called Alkeran

    Given IV

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMTMI

  • Total Marrow IrradiationRadiation

    Undergo IMTMI

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called HSC, HSCT

    Undergo allogeneic PBSCT

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

    Undergo allogeneic PBSCT

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic BMT

    Undergo allogeneic BMT

  • TacrolimusDrug

    Also called Advagraf, FK 506

    Given IV or PO

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02333162
Study groupRoleWhat they receive
Treatment (IMTMI, combination chemotherapy, PBSCT or BMT)ExperimentalCONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI BID for 2 to 5 days between days -7 to -3. TRANSPLANT: Patients undergo allogeneic PBSCT or BMT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60.
Receives: Drug: Fludarabine Phosphate; Drug: Melphalan; Radiation: Intensity-Modulated Radiation Therapy; Radiation: Total Marrow Irradiation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. MTD of conditioning regimen defined as any grade III or higher dose-limiting toxicity, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: Up to 30 days post second allo-SCT

Secondary outcomes (6)

  1. Overall incidence of adverse events, graded according to the NCI CTCAE version 4.0

    Measured: Up to 2 years

  2. Transplant related mortality

    Measured: Day 100

  3. Time to neutrophil engraftment

    Measured: First day in which the ANC is > 500/mm^3 for 3 consecutive days

  4. Time to platelet engraftment

    Measured: First day the platelet count is > 20,000/mm^3 without transfusion support for 7 consecutive days

  5. overall survival (OS)

    Measured: Up to 2 years

  6. event-free-survival (EFS)

    Measured: Up to 2 years

Timeline

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

  1. First posted7 Jan 2015 (estimated)
  2. Study start5 Dec 2014
  3. Primary completion1 Dec 2028 (estimated)
  4. Study completion1 Dec 2028 (estimated)

Why it stopped: Enrollment on hold pending amendment

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
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02333162
Sponsor's protocol ID
IRB14-0709
Other IDs
NCI-2014-02469, IRB14-0709, P30CA014599
Status last verified
Mar 2026
First submitted
5 Jan 2015
Last updated
30 Mar 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine Phosphate, Melphalan and Intensity-Modulated Radiation Therapy in people with Previously Treated Myelodysplastic Syndrome and Recurrent Adult Acute Lymphoblastic Leukemia, run by University of Chicago 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 16 inclusion and 0 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: paused, as of the sponsor's last update on 30 Mar 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?

Results are not available in the source record.

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?

MTD of conditioning regimen defined as any grade III or higher dose-limiting toxicity, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: Up to 30 days post second allo-SCT). 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 NCT02333162.

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 30 Mar 2026.

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