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ED-TBI Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory AML And Advanced MDS (ED-TBI)

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ClinicalTrials.gov Identifier: NCT01709396
Recruitment Status : Suspended (initial on hold due to space but now permanently suspended due to futility.)
First Posted : October 18, 2012
Last Update Posted : January 12, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

Acute myeloid leukemia (AML) is a rapidly fatal malignancy of the bone marrow. It can be treated with chemotherapy alone, in some cases, but in the majority of cases, the only treatment that can cure the disease is an allogeneic stem cell transplant, with a cure rate of 30-40%. In another subset, the disease is less responsive to chemotherapy and in these aggressive forms, its cure rate is no better than 20% beyond 2 years, and is usually rapidly fatal within 6 months.

Therefore, for this most aggressive form of the disease, modifications to the transplant protocol are required in order to try to improve on these poor results. There are a number of areas within the transplant protocol on which modifications can be made in order to achieve these goals. These include: higher doses of chemotherapy and or radiation; alterations of the new bone marrow graft; and alterations of the immune suppression, enhancing the graft vs. leukemia effect. By focusing on one or more of these components, one might be able to enhance the anti-leukemic aspect of the treatment resulting in a more successful outcome.

One aspect the investigators, in Ottawa, have focused on is the initial intensive conditioning regimen, specifically the radiation component. It is the investigators belief that in the most resistant disease it is important to use the highest tolerable anti-leukemic treatment upfront, specifically, enhancing the radiation component of the initial conditioning regimen. Previous studies have suggested that higher doses of radiation might be more effective at eliminating the disease, however, toxicity and logistics of delivering the radiation have limited its use. Technical advances in the delivery of radiation have now permitted the safer use of high doses of radiation.

Through modifications to the transplant procedure, the investigators believe that they can deliver higher doses of radiation safely and this will translate into improved outcomes in this high-risk subgroup of patients with AML.

Study Objectives

The goal of this study is to determine if a total dose of 18Gy ED-TBI followed by an alloHSCT for patients with refractory AML will result in an improved progression-free survival.

Condition or disease Intervention/treatment Phase
Acute Leukemia Myelodysplastic Syndrome Radiation: ED-TBI Phase 2

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Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Extended Dose - Total Body Irradiation Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory Acute Leukemia And Advanced Myelodysplastic Syndrome
Study Start Date : January 2012
Primary Completion Date : January 2016
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 18 cGY ED-TBI
18 cGY ED-TBI followed by an allogenic done marrow transplant
Radiation: ED-TBI
Patients will receive 18Gy ED-TBI in 8 fractions of 2.25 Gy each, twice/day for 4 days. Following the final fraction of TBI and an allogeneic hematopoietic stem cell graft.

Outcome Measures

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 1 year post allogenic transplant ]
    The primary objective of this study is to determine the progression-free survival at 1 year, post alloHSCT, after ED-TBI followed by an alloHSCT for patients with refractory AML

Secondary Outcome Measures :
  1. Engraftment [ Time Frame: Within 100 day post transplant ]
    The time to neutrophil and platelet engraftment following ED-TBI and alloHSCT

  2. Morbidity/Mortality [ Time Frame: day 30, day 100, day 180 post transplant ]
    • The day 30 morbidity (frequency, severity and affected organ function) of ED-TBI
    • The day 30 mortality associated with ED-TBI and alloHSCT.
    • The day 100 morbidity (frequency, severity and affected organ function) of ED-TBI
    • The day 100 mortality associated with ED-TBI and alloHSCT.
    • The late (> 6 month and >1 year) morbidity and mortality of ED-TBI/alloHSCT

  3. Relapse [ Time Frame: 5 years post transplant ]
    • Relapse rate after alloHSCT
    • The pattern of relapse (blood and marrow vs. extramedullary)
    • The overall survival

  4. GVHD [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ]
    Incidence and severity of acute and chronic GVHD

Other Outcome Measures:
  1. Evaluation of Safety [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ]

    All patients who receive at least one fraction of ED-TBI will be used in the safety analysis.

    • The incidence of adverse and serious adverse events will be tabulated by, severity and relationship to the treatment.
    • Adverse and serious adverse events will be monitored on an ongoing basis by the investigators.
    • Adverse events will be categorized using the CTCAE v.4. Adverse events will be summarized at the following intervals post stem cell transplant: day 30, day 100, 180, 365 and 730.

  2. Evaluation of Efficacy [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ]
    Objective data to determine CR rate, rate of relapse, time-to-progression and overall survival will be collected and reported.

  3. Duration of Study [ Time Frame: 2-3 years ]
    Approximately, 5 patients from our institution will be eligible per year. Additional patients from cooperating centers could, potentially, add another 5 patients/year. Therefore, the duration of accrual is expected to be between 2-3 years.

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • All subjects must meet all of the following criteria to be eligible for the study. These will be evaluated within the four weeks prior to enrolment.
  • Subject must have primary refractory AML, secondary AML, relapsed AML or high risk MDS
  • Primary refractory AML is defined as:

A blast count in the bone marrow of >5% or the presence of any amount of circulating blasts, in the peripheral blood, after 1 cycle of induction chemotherapy.

  • Secondary AML is defined as:

AML, except acute promyelocytic leukemia, arising from any haematological disease or from the exposure to chemotherapy for another unrelated malignancy.

  • Relapsed AML is defined as:

Relapse (>5% blasts in the marrow) after having achieved a CR, of any duration.

  • High risk myelodysplasia is defined as:

Myelodysplastic syndrome as defined by the WHO criteria with an international prognostic score (IPSS) of intermediate-2 or high

  • Subjects must have a score of ≥2 on the scoring system for hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure
  • Subjects must meet institutional guidelines for an alloHSCT.
  • Subjects must have a matched related or a well- or partially-matched unrelated donor, acceptable to institutional guidelines who can donate either peripheral blood or bone marrow hematopoietic stem cells.
  • Subjects must be of age ≥18 and ≤60 years.
  • Subjects must have an ECOG performance score of 0,1, or 2
  • Subjects must have the ability to comply with the protocol visit schedule and other protocol requirements.

Exclusion Criteria

  • Subjects who have a score of < 2 on the scoring system for hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure
  • Subjects who previously received an autoHSCT or alloHSCT
  • Subjects who have previously received radiation therapy
  • Subjects with a prior nephrectomy or a known history of a single kidney.
  • Subjects with HIV-seropositivity.
  • Subjects with a recent history of alcohol or drug abuse.
  • Pregnant or lactating female subjects.
  • Subject whose only donor is an umbilical cord donor
  • Subjects whose only donor is an unrelated mismatched donor, according the recently published CIBMTR criteria.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01709396

Canada, Ontario
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada, K1H8L6
Sponsors and Collaborators
Ottawa Hospital Research Institute
Principal Investigator: Mitchell Sabloff The Ottawa Hospital - Ottawa Hospital Research Institute
More Information

Additional Information:
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01709396     History of Changes
Other Study ID Numbers: 2011064-01
First Posted: October 18, 2012    Key Record Dates
Last Update Posted: January 12, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Acute Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Disease Attributes