Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes

NCT03235973 | Unknown Phase 1 DMC

• 1 other identifier: CEREAL-IPC 2016-010
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators focused on patients with refractory acute leukemia or MDS and designed a phase 1 trial of escalated cladribine doses in the Cla-Flu-Bu RTC regimen using PK-guided myeloablative busulfan doses. This scheme allows combining different optimization of RTC experienced over years (Flu-Bu RTC, PK-guided myeloablative busulfan doses, a second purine analog cladribine) to approach a specific platform to treat refractory diseases.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphoblastic, Acute

Keywords

refractory acute leukemia; refractory myelodysplastic syndrome; cladribine dose escalation

Outcome Measures

Primary Outcomes (1)

• estimation of the maximal tolerable dose,if any,and recommended phase II dose of cladribine administered as in combination with fludarabine and PK-guided IV busulfan prior Allo-HSCT for refractory acute leukemia and myelodysplastic syndrome (MDS)

  Occurrence ratio of dose-limiting toxicity defined as any grade ≥ 3 toxicity according to CTCAE (version 4.03 ) attributable to conditioning regimen (extra-medullary toxicity), considered to be related or probably related to the Cla-Fu-Bu RTC by the investigator.

  30 days after Allo-HSCT

Secondary Outcomes (4)

• Cumulative incidence of acute Graft versus host disease

  100 days

• Cumulative incidence of chronic Graft versus host disease

  1 year

• Cumulative incidence of relapse

  1 year

• Cumulative incidence of Non Relapse Mortality

  100 days, 1 year

Study Arms (1)

Fludarabine-Cladribine-Busulfan conditioning regimen

EXPERIMENTAL

Drug: Fludarabine-Cladribine-Busulfan conditioning regimen

Interventions

Fludarabine-Cladribine-Busulfan conditioning regimen DRUG

Conditioning regimen will be performed from day -6 to day -2 and contains: * Fludarabine 10 mg/m²/d during 5 days (day-6 to day-2). * Cladribine during 5 days (day-6 to day-2) at one the following define dose level: * Dose 1: 10 mg/m²/d * Dose 2: 15 mg/m²/d * Dose 3: 20 mg/m²/d * Dose 4: 25 mg/m²/d * IV busulfan will be given on day-6 using fixed dose as following: * If age ≤ 60 years: starting dose of 130 mg/m² * If age \> 60 years: starting dose of 100 mg/m² No busulfan will be administered at day-5, allowing the pharmacokinetic (PK) analyses . Subsequent infusion of IV busulfan will be performed from day-4 to day-2 at the dose recommended by PK analyses

Fludarabine-Cladribine-Busulfan conditioning regimen

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• ECOG 0 or 1
• Acute leukemia (AML or ALL) without criteria for CR or high risk MDS without criteria for CR
• Availability of a donor among following oHLA identical sibling oHaploidentical donor o10/10 or 9/10 allele-level HLA matched unrelated donor
• Signed informed consent
• Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen

You may not qualify if:

• Contraindication for Allo-HSCT
• Cord blood Allo-HSCT
• Current active disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen.
• Renal failure with creatinine clearance \< 30 ml/ min
• Decompensated haemolytic anaemia
• Hypersensitivity to an active substance or to any of the excipients
• Acute urinary infection
• Pre-existing haemorrhagic cystitis
• Woman of childbearing potential not using an effective contraception .
• Pregnant or lactating women
• Any serious concurrent uncontrolled medical disorder
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• Institut Paoli-Calmettes: lead

Study Sites (1)

Institut Paoli-Calmettes

Marseille, Bouches-du-Rhône, 13009, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Study Officials

• Raynier Devillier, MD,PhD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominique Genre, MD

CONTACT

+33491223778; drci.up@ipc.unicancer.fr

Jihane Pakradouni, PharmD, PhD

CONTACT

+33491223778; drci.up@ipc.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: August 1, 2017
• Study Start: April 28, 2018
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2021
• Last Updated: June 28, 2018

Record last verified: 2018-06

Locations

FR (1)