Allo-Allo Tandem Bone Marrow Transplant (BMT)

Refractory Acute Leukemia Clinical Trial

— AATT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00984412
• Other study ID #: MYS-07-HMO-CTIL
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: September 6, 2009
• Last updated: February 18, 2016
• Start date: November 2009
• Est. completion date: November 2020

Study information

• Verified date: February 2016
• Source: Hadassah Medical Organization
• Contact: Michael Y Shapira, MD
• Phone: 972-2-6778351
• Email: shapiram[@]hadassah.org.il
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: November 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 50 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Refractory Acute Leukemia

Intervention

Procedure:
• Allogeneic hematopoietic stem-cell-transplantation
2 allogeneic BMTs 6 weeks apart

Locations

Country	Name	City	State
Israel	Hadassah Medical Organization	Jerusalem

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplant-related mortality (TRM) of SCT II.		240d	Yes
Primary	Transplant-related toxicity (TRT) of SCT II.		240d	Yes
Secondary	Day of neutrophil engraftment at SCT II		240d	Yes
Secondary	Day of platelet engraftment >20x109/L at SCT II		240d	Yes
Secondary	Day of platelet engraftment >50x109/L at SCT II		240d	Yes
Secondary	Acute GVHD occurrence = 2 following SCT II		100d	Yes
Secondary	Time to acute GVHD following SCT II		100d	Yes
Secondary	GVHD grade following SCT II		240d	Yes
Secondary	Overall survival at 180 days from SCT II		180d	Yes
Secondary	Disease free survival at 180 days SCT II		180d	Yes
Secondary	Infections incidence		240d	Yes
Secondary	Immune reconstitution		240d	Yes