Phase 2 study of a reduced-toxicity myeloablative conditionning regimen using fludarabine and full doses of IV busulfan in pediatric patients not eligible for standard myeloablative conditioning regimens. - FB4-PEDIA

Phase 1

• Conditions: Hematological malignancy; MedDRA version: 14.0Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-004764-30-FR
• Lead Sponsor: CHU Nantes

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-18
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

- Children and adolescents under the age of 18 years
- Availability of an HLA identical family donor or an HLA-matched unrelated donor (10/10 or 9/10 if the mismatch level is at HLACw for an unrelated donor)
- Informed consent signed by patient’s legal representative, parent(s) or guardian.
- Diagnosis of a hematologic malignancy which is a candidate for allo-HSCT, but not eligible for standard or conventional myeloablative conditioning regimens because of high risk for toxicity.
- Are considered as criteria of eligibility for non-standard or conventional myeloablative conditioning:
* a history of autologous or allogeneic stem cell transplantation
* comorbidities or medical history predictive of a prohibitive rate of TRM and toxicity with the use of standard high dose chemotherapy and / or radiotherapy.
- Eligible hematologic malignancies treatable with allogeneic hematopoietic cell transplantation include: acute and chronic leukemias, myelodysplasia [MDS], or lymphomas.
? Patients with ALL are required to be in morphologic remission (<5%blasts), whereas patients with acute myelogenous leukemia (AML) not in stringent CR are allowed (Patients not in CR should be discussed with the PI on a case per case basis).
? Patients with juvenile myelomonocytic leukemia (JMML) and MDS are required to have less than 5% blasts, and those with chronic myelogenous leukemia have to be in first chronic phase, accelerated phase, or subsequent chronic phase with less than 5% blasts.

Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Patient has been administered any other systemic chemotherapeutic drug (including Gemtuzumab) within 21 days prior to trial enrollment and start of the conditioning regimen. Hydroxyurea is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed leptomeningeal disease, that has been in remission for at least 3 months prior to enrollment on this study.
- Active infection. Protocol PI will be final arbiter if there is uncertainty regarding whether a previous infection is resolved.
- Age =18 years
- A donor who is HLA mismatched at the level of more than one locus.
- Poor performance status
- Life expectancy is severely limited by concomitant illness and expected to be <12 weeks.
- Left ventricular ejection fraction <30%. Uncontrolled arrhythmias or symptomatic cardiac disease.
- Symptomatic pulmonary disease. FEV1, FVC and DLCO <30% of expected corrected for hemoglobin.
- Creatinine clearance less than 30 mL/m per 1.73 m2 or requiring dialysis
- Evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
- Effusion or ascites >1L prior to drainage.
- HIV-positive.
- Female pregnancy (all females of child-bearing-potential).
- Patient’s legal representative, parent(s) or guardian not able to sign informed consent.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess transplant-related mortality (TRM) at one year after allogeneic hematopoietic stem cell transplantation prepared by a reduced toxicity myeloablative conditioning regimen;Secondary Objective: - Incidence of engraftment (neutrophils and platelets recovery after transplantation)<br>- Incidence and severity of acute GVHD<br>- Incidence and severity of chronic GVHD<br>- Rate of disease relapse at one year after transplantation<br>- Disease-free survival at one year after transplantation<br>- Overall Survival at one year after transplantation<br>- Immune Recovery (to be determined in a subgroup of patients)<br>;Primary end point(s): Evaluation of the cumulative incidence of TRM at 12 months after transplantation

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Incidence of engraftment defined as the first day of neutrophil (>500/µl for 3 consecutive days). Engraftment failure is defined as neutrophil <500/µl at day+42 after allo-SCT.<br>- Evaluation of overall (OS) and disease-free survival (DFS) at 1 year after transplantation<br>- Cumulative incidence of relapse, death from disease, and non-relapse mortality (NRM)<br>- Cumulative incidences and severity of acute and chronic Graft-versus-Host disease<br>- Immune Recovery parameters <br>