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

Primary Purpose

Refractory Acute Leukemia

Status

Unknown status

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

Allogeneic hematopoietic stem-cell-transplantation

About this trial

This is an interventional treatment trial for Refractory Acute Leukemia

Eligibility Criteria

3 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).
A donor willing and capable of donating peripheral blood stem cells and preferably also bone marrow cells, and lymphocytes if indicated.
Each patient / patient's guardian must sign written informed consent.
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:

Not fulfilling any of the inclusion criteria.
In complete or very good partial remission.
Beyond 2nd relapse.
Received > 2 lines of salvage therapy.
Active CNS involvement of the leukemia
Active life-threatening infection.
Overt untreated infection.
HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis.
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).
Previous autologous or allogeneic stem cell transplantation.
Inability to comply with study requirements.

Sites / Locations

Hadassah Medical OrganizationRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AATT

Arm Description

Outcomes

Primary Outcome Measures

Transplant-related mortality (TRM) of SCT II.

Transplant-related toxicity (TRT) of SCT II.

Secondary Outcome Measures

Day of neutrophil engraftment at SCT II

Day of platelet engraftment >20x109/L at SCT II

Day of platelet engraftment >50x109/L at SCT II

Acute GVHD occurrence ≥ 2 following SCT II

Time to acute GVHD following SCT II

GVHD grade following SCT II

Overall survival at 180 days from SCT II

Disease free survival at 180 days SCT II

Infections incidence

Immune reconstitution

Full Information

NCT ID

NCT00984412

First Posted

September 6, 2009

Last Updated

February 18, 2016

Sponsor

Hadassah Medical Organization

1. Study Identification

Unique Protocol Identification Number

NCT00984412

Brief Title

Allo-Allo Tandem Bone Marrow Transplant (BMT)

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Unknown status

Study Start Date

November 2009 (undefined)

Primary Completion Date

April 2020 (Anticipated)

Study Completion Date

November 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hadassah Medical Organization

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory Acute Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AATT

Arm Type

Experimental

Intervention Type

Procedure

Intervention Name(s)

Allogeneic hematopoietic stem-cell-transplantation

Intervention Description

2 allogeneic BMTs 6 weeks apart

Primary Outcome Measure Information:

Title

Transplant-related mortality (TRM) of SCT II.

Time Frame

240d

Title

Transplant-related toxicity (TRT) of SCT II.

Time Frame

240d

Secondary Outcome Measure Information:

Title

Day of neutrophil engraftment at SCT II

Time Frame

240d

Title

Day of platelet engraftment >20x109/L at SCT II

Time Frame

240d

Title

Day of platelet engraftment >50x109/L at SCT II

Time Frame

240d

Title

Acute GVHD occurrence ≥ 2 following SCT II

Time Frame

100d

Title

Time to acute GVHD following SCT II

Time Frame

100d

Title

GVHD grade following SCT II

Time Frame

240d

Title

Overall survival at 180 days from SCT II

Time Frame

180d

Title

Disease free survival at 180 days SCT II

Time Frame

180d

Title

Infections incidence

Time Frame

240d

Title

Immune reconstitution

Time Frame

240d

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). A donor willing and capable of donating peripheral blood stem cells and preferably also bone marrow cells, and lymphocytes if indicated. Each patient / patient's guardian must sign written informed consent. 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: Not fulfilling any of the inclusion criteria. In complete or very good partial remission. Beyond 2nd relapse. Received > 2 lines of salvage therapy. Active CNS involvement of the leukemia Active life-threatening infection. Overt untreated infection. HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis. 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). Previous autologous or allogeneic stem cell transplantation. Inability to comply with study requirements.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Y Shapira, MD

Phone

972-2-6778351

shapiram@hadassah.org.il

Facility Information:

Facility Name

Hadassah Medical Organization

City

Jerusalem

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arik Tzukert, DMD

Phone

00 972 2 6776095

arik@hadassah.org.il

First Name & Middle Initial & Last Name & Degree

Hadas Lamberg, PhD

Phone

00972 2 6777572

Ihadas@hadassah.org.il

First Name & Middle Initial & Last Name & Degree

Michael Y Shapira, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

33512419

Citation

Schmitz N, Truemper L, Bouabdallah K, Ziepert M, Leclerc M, Cartron G, Jaccard A, Reimer P, Wagner E, Wilhelm M, Sanhes L, Lamy T, de Leval L, Rosenwald A, Roussel M, Kroschinsky F, Lindemann W, Dreger P, Viardot A, Milpied N, Gisselbrecht C, Wulf G, Gyan E, Gaulard P, Bay JO, Glass B, Poeschel V, Damaj G, Sibon D, Delmer A, Bilger K, Banos A, Haenel M, Dreyling M, Metzner B, Keller U, Braulke F, Friedrichs B, Nickelsen M, Altmann B, Tournilhac O. A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL. Blood. 2021 May 13;137(19):2646-2656. doi: 10.1182/blood.2020008825.

Results Reference

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Allo-Allo Tandem Bone Marrow Transplant (BMT)

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