Allo-Allo Tandem Bone Marrow Transplant (BMT)

NCT ID: NCT00984412

Last Updated: 2016-02-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2020-11-30

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.

Conditions

Refractory Acute Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AATT

Group Type: EXPERIMENTAL

Allogeneic hematopoietic stem-cell-transplantation

Intervention Type: PROCEDURE

2 allogeneic BMTs 6 weeks apart

Interventions

Allogeneic hematopoietic stem-cell-transplantation

2 allogeneic BMTs 6 weeks apart

Intervention Type: PROCEDURE

Eligibility 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.

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.

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hadassah Medical Organization

OTHER

Sponsor Role: lead

Responsible Party

SHAPIRA MICHAEL

Prof shapira

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hadassah Medical Organization

Jerusalem, , Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Michael Y Shapira, MD

Role: CONTACT

shapiram@hadassah.org.il

972-2-6778351

Facility Contacts

Arik Tzukert, DMD

Role: primary

arik@hadassah.org.il

00 972 2 6776095

Hadas Lamberg, PhD

Role: backup

Ihadas@hadassah.org.il

00972 2 6777572

References

Tournilhac O, Altmann B, Friedrichs B, Bouabdallah K, Leclerc M, Cartron G, Turlure P, Reimer P, Wagner-Drouet E, Sanhes L, Houot R, Roussel M, Kroschinsky F, Dreger P, Viardot A, de Leval L, Rosenwald A, Gaulard P, Wulf G, Villate A, Latiere C, Elmaagacli A, Glass B, Poeschel V, Damaj G, Sibon D, Durot E, Bilger K, Banos A, Haenel M, Dreyling M, Keller U, Tiab M, Drenou B, Cornillon J, Nguyen S, Robin M, Nickelsen M, Trumper L, Lenz G, Ziepert M, Schmitz N; French Lymphoma Study Association (LYSA), the Societe Francophone de greffe de moelle et Therapie Cellulaire (SFGM-TC), and the German Lymphoma Alliance (GLA). Long-Term Follow-Up of the Prospective Randomized AATT Study (Autologous or Allogeneic Transplantation in Patients With Peripheral T-Cell Lymphoma). J Clin Oncol. 2024 Nov 10;42(32):3788-3794. doi: 10.1200/JCO.24.00554. Epub 2024 Sep 13.

Reference Type: DERIVED

PMID: 39270145 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33512419 (View on PubMed)

Other Identifiers

MYS-07-HMO-CTIL

Identifier Type: -

Identifier Source: org_study_id