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Allo-Allo Tandem Bone Marrow Transplant (BMT) (AATT)

This study is currently recruiting participants.
Verified February 2011 by Hadassah Medical Organization
Sponsor:
Information provided by:
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT00984412
First received: September 6, 2009
Last updated: March 1, 2011
Last verified: February 2011
History of Changes
  Purpose

Refractory acute leukemia (AL) occurs in a significant percentage of the AL patients and presents a therapeutic challenge. Allogeneic stem cell transplantation (allo-SCT) is the only curative option for these patients. Although many of the patients with refractory AL that undergo myeloablative SCT initially achieve complete remission, most relapse later on, and the long-term disease free survival is poor. In order to achieve better leukemic control, most transplant centers employ post transplant early withdrawal of the anti-GVHD immunosuppression; hence exposing the patients to high risk of GVHD associated morbidity and mortality. This study will try to address this common scenario, namely early and late relapse. The investigators will try to attain better leukemic control by re-inducing the patients, 6 weeks after the 1st transplant with further myeloablative treatment (busulfex and thiotepa) followed by allogeneic stem cell support (transplant II).


Condition Intervention Phase
Refractory Acute Leukemia
 Procedure: Allogeneic hematopoietic stem-cell-transplantation
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allo-allo Tandem Matched Stem Cell Transplantation (AATT) for the Treatment of Patients With Refractory Acute Leukemia; a Feasibility Phase I/II Study

Resource links provided by NLM:

MedlinePlus related topics: Leukemia
Drug Information available for: Tandem
U.S. FDA Resources

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Transplant-related mortality (TRM) of SCT II. [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Transplant-related toxicity (TRT) of SCT II. [ Time Frame: 240d ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Day of neutrophil engraftment at SCT II [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Day of platelet engraftment >20x109/L at SCT II [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Day of platelet engraftment >50x109/L at SCT II [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Acute GVHD occurrence ≥ 2 following SCT II [ Time Frame: 100d ] [ Designated as safety issue: Yes ]
  • Time to acute GVHD following SCT II [ Time Frame: 100d ] [ Designated as safety issue: Yes ]
  • GVHD grade following SCT II [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Overall survival at 180 days from SCT II [ Time Frame: 180d ] [ Designated as safety issue: Yes ]
  • Disease free survival at 180 days SCT II [ Time Frame: 180d ] [ Designated as safety issue: Yes ]
  • Infections incidence [ Time Frame: 240d ] [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Time Frame: 240d ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: November 2009
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AATT Procedure: Allogeneic hematopoietic stem-cell-transplantation
2 allogeneic BMTs 6 weeks apart

Detailed Description:

The effects of feasibility oExperimental design and methods f allo-allo tandem matched stem cell transplantation (AATT) in patients with refractory leukemia will be evaluated in a clinical setting. The current study is limited only for patients with refractory disease that received and failed up to 2 lines of salvage therapy, in good performance status and younger than 50 years old. Only patients that will achieve complete remission after transplant I, will have no major organ dysfunction and with acceptable performance status, will be treated with transplant II. Close monitoring with strict stopping rules including in case of excess transplant related morality, acute or chronic GVHD or graft failure will be employed.

Treatment schedule:

15 patients (divided into 2 cohorts, see below) with matched family member or unrelated donor will be included in single arm open phase I/II trial.

Conditioning protocol:

All patients will be prepared by the same sequential conditioning protocols:

Transplant I: Cy-TBI followed by Transplant II: Busulfan-thiotepa.

  Eligibility

Ages Eligible for Study:   3 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient age 3-50 years old with refractory acute leukemia (primary refractory or refractory relapse I or II) unresponsive to up to 2 salvage lines with a matched donor (related or unrelated, matched defined as 8/8 HLA matching).
  2. A donor willing and capable of donating peripheral blood stem cells and preferably also bone marrow cells, and lymphocytes if indicated.
  3. Each patient / patient's guardian must sign written informed consent.
  4. Patients must have an ECOG PS ≤ 1; Creatinine <1.5 mg/dl; Ejection fraction >45%; DLCO >70% of predicted; Serum bilirubin <2 mg/dl; elevated GPT or GOT < 2 x normal values before transplant I.

Exclusion Criteria:

  1. Not fulfilling any of the inclusion criteria.
  2. In complete or very good partial remission.
  3. Beyond 2nd relapse.
  4. Received > 2 lines of salvage therapy.
  5. Active CNS involvement of the leukemia
  6. Active life-threatening infection.
  7. Overt untreated infection.
  8. HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis.
  9. Donor contraindication (HIV seropositive confirmed by Western Blot, Hepatitis B antigenemia, HCV, evidence of bone marrow disease, unable to donate bone marrow or peripheral blood due to concurrent medical condition).
  10. Previous autologous or allogeneic stem cell transplantation.
  11. Inability to comply with study requirements.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00984412

Contacts
Contact: Michael Y Shapira, MD 972-2-6778351 shapiram@hadassah.org.il

Locations
Israel
Hadassah Medical Organization Recruiting
Jerusalem, Israel
Contact: Arik Tzukert, DMD     00 972 2 6776095     arik@hadassah.org.il    
Contact: Hadas Lamberg, PhD     00972 2 6777572     Ihadas@hadassah.org.il    
Principal Investigator: Michael Y Shapira, MD            
Sponsors and Collaborators
Hadassah Medical Organization
  More Information

No publications provided

Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT00984412     History of Changes
Other Study ID Numbers: MYS-07-HMO-CTIL
Study First Received: September 6, 2009
Last Updated: March 1, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Additional relevant MeSH terms:
Leukemia
Acute Disease
Neoplasms by Histologic Type
 Neoplasms
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013