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

NCT01709396 | Suspended Phase 2 DMC

• 1 other identifier: 2011064-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  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

  1 year post allogenic transplant

Secondary Outcomes (4)

• Engraftment

  Within 100 day post transplant

• Morbidity/Mortality

  day 30, day 100, day 180 post transplant

• Relapse

  5 years post transplant

• GVHD

  day 30, day 100, 180, 365 and 730 post transplant

Other Outcomes (3)

• Evaluation of Safety

  day 30, day 100, 180, 365 and 730 post transplant

• Evaluation of Efficacy

  day 30, day 100, 180, 365 and 730 post transplant

• Duration of Study

  2-3 years

Study Arms (1)

18 cGY ED-TBI

EXPERIMENTAL

18 cGY ED-TBI followed by an allogenic done marrow transplant

Radiation: ED-TBI

Interventions

ED-TBI RADIATION

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.

18 cGY ED-TBI

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H8L6, Canada

Location

Related Links

• Ottawa Hospital Research Institute

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Mitchell Sabloff

  The Ottawa Hospital - Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 18, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2018
• Last Updated: January 12, 2017

Record last verified: 2017-01

Locations

CA (1)