Extended Dose - Total Body Irradiation Followed By Allogeneic Stem Cell Transplantation For The Treatment Of Refractory Acute Leukemia And Advanced Myelodysplastic Syndrome (ED-TBI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Ottawa Hospital Research Institute
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01709396
First received: October 12, 2012
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Refractory AML, Secondary AML, Relapsed AML or High Risk MDS
HLA MRD or Volunteer Well or Partially URD
Radiation: ED-TBI
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 1 year post allogenic transplant ] [ Designated as safety issue: Yes ]
    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:
  • Engraftment [ Time Frame: Within 100 day post tranplant ] [ Designated as safety issue: Yes ]
    The time to neutrophil and platelet engraftment following ED-TBI and alloHSCT

  • Morbidity/Mortality [ Time Frame: day 30, day 100, day 180 post tranplant ] [ Designated as safety issue: No ]
    • 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

  • Relapse [ Time Frame: 5 years post transplant ] [ Designated as safety issue: No ]
    • Relapse rate after alloHSCT
    • The pattern of relapse (blood and marrow vs. extramedullary)
    • The overall survival

  • GVHD [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: Yes ]
    Incidence and severity of acute and chronic GVHD


Other Outcome Measures:
  • Evaluation of Safety [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: Yes ]

    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.

  • Evaluation of Efficacy [ Time Frame: day 30, day 100, 180, 365 and 730 post transplant ] [ Designated as safety issue: No ]
    Objective data to determine CR rate, rate of relapse, time-to-progression and overall survival will be collected and reported.

  • Duration of Study [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 20
Study Start Date: January 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 18Gy ED-TBI followed by an alloHSCT 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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709396

Contacts
Contact: Mitchell Sabloff 613-737-8899 ext 71284
Contact: Mai Le 613-737-8899 ext 79376

Locations
Canada, Ontario
The Ottawa Hospital - General Campus Recruiting
Ottawa, Ontario, Canada, K1H8L6
Contact: Mitchell Sabloff, Dr    613-737-8899 ext 71284      
Contact: Mai Le    613-737-8899 ext 79376      
Principal Investigator: Mitchell Sabloff, Dr         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: Mitchell Sabloff The Ottawa Hospital - Ottawa Hospital Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01709396     History of Changes
Other Study ID Numbers: 2011064-01
Study First Received: October 12, 2012
Last Updated: October 16, 2012
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014