PHASE II STUDY OF TOTAL MARROW AND LYMPHOID IRRADIATION (TMLI) GIVEN IN COMBINATION WITH CYCLOPHOSPHAMIDE AND ETOPOSIDE (VP-16) AS CONDITIONING FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH-RISK ACUTE LYMPHOCYTIC OR MYELOGENOUS LEUKEMIA

Phase 1

• Conditions: Acute Lymphocytic or Myelogenous Leukemia; MedDRA version: 20.1Level: LLTClassification code 10024330Term: Leukemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004270-22-IT
• Lead Sponsor: IRCCS-A.O.U. SAN MARTINO-IST

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-17
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

•Age =18 to =60 years
•Karnofsky performance status must be =70%
•Patients with acute lymphocytic leukemia or acute myelogenous leukemia who are not in first remission or second remission, i.e. after failing induction therapy, or in relapse, or beyond second remission.
•All candidates for this study must have an HLA (A,B,C,DR) identical sibling who is willing to donate bone marrow or primed blood stem cells, a 10/10 allele matched unrelated donor.
•Patients must undergo cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm, and an ejection fraction of =50% established by MUGA or echocardiogram.
•Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance > 80ml/min.
•Patients must have bilirubin of less than or equal to 1.5mg/dL and should also have an SGOT and SGPT less than 5 times the upper limit of normal
•Pulmonary function tests including DLCO will be performed. FEV1and DLCO should be greater than 50% of predicted normal value.
•The time from the end last induction or re-induction attempt should be greater than or equal to 14 days.
•All patients must have a psychosocial evaluation prior to transplant as per COH SOP
•All subjects must have the ability to understand and the willingness to sign a written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patients who have received a prior autologous or allogeneic transplant are excluded
•Uncontrolled inter-current illness including, but not limited to ongoing or active or poorly controlled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements.
•Pregnant and lactating women are excluded from this study.
•Patients who do not agree to practice effective forms of contraception.
•Patients who received radiation therapy that would exclude them from the use of total body irradiation are ineligible and individual patients who have received prior radiation must be presented to the study PI for eligibility determination.
•Patients with active 2nd malignancies other than AML, ALL or MDS.
•Any psychiatric, social or compliance issues that, in the treating physician opinion, will interfere with completion of the transplant treatment and follow up.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the anti-tumor activity of TMLI given in combination with cyclophosphamide (Cy) and etoposide (VP-16) as assessed by 2-year progression-free survival (PFS).;Secondary Objective: Estimate overall survival (OS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.<br>Evaluate early/late toxicities/complications by organ/severity (including acute/chronic GVHD infection), and characterize by organ dose/dose volume.;Primary end point(s): The primary study endpoint is 2-year progression-free survival (PFS). PFS will be estimated from the start of treatment to the date of death, disease relapse/progression, or date of last contact using the Kaplan-Meier method.;Timepoint(s) of evaluation of this end point: Two years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): CR proportion at day 30; Non- relapse mortality; Incidence of Infetion; Toxicitie and adverse events; Acute GVHD; Chronic GVHD; •Overall Survival; •EM and BM relapse/progression;Timepoint(s) of evaluation of this end point: 26 months; 7 years; 27 months; 27 months; 27 months; 7 years; 7years; 7 years