Comparing two conditioning regimens for allogeneic hematopoietic cell transplantation
Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning: a Phase II Randomized Study From the Belgian Hematology Society (BHS)
This study is testing two different treatment plans for patients with blood cancers who are getting stem cell transplants from matched donors to see which one helps them stay healthy longer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 114 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | University of Liege Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 10 sites (Antwerp and 9 other locations) |
| Trial ID | NCT03852407 on ClinicalTrials.gov |
What this trial studies
This multicenter, randomized, open-label phase II study aims to compare two conditioning regimens, FM-PTCy and FM-ATG, in patients with hematological malignancies who have HLA-matched donors. A total of 114 eligible patients will be randomized in a 1:1 ratio between the two arms, with stratification based on donor type. The study will follow participants for 5 years, with an additional 10 years for long-term outcomes related to graft versus host disease, disease status, and quality of life. The goal is to improve the 2-year cumulative graft rejection-free survival rate from 30% to 45%.
Who should consider this trial
Good fit: Ideal candidates include patients with hematological malignancies such as acute myeloid leukemia, myelodysplastic syndromes, and chronic myeloid leukemia in remission who have HLA-matched donors.
Not a fit: Patients with rapidly progressing hematological malignancies or those who are not eligible for standard allogeneic transplantation may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could significantly improve survival rates and quality of life for patients undergoing allogeneic hematopoietic cell transplantation.
How similar studies have performed: Other studies have shown promise in using reduced-intensity conditioning regimens for hematological malignancies, making this approach both relevant and potentially impactful.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
Patients V.1.1. Diseases
Hematological malignancies confirmed histologically:
* AML in morphological CR or not in morphological CR but not rapidly progressing (i.e. no need to give treatments such as hydroxyurea to maintain WBC count \< 10 000 x109/mL);
* MDS;
* CML in CP or AP;
* MPD not in blast crisis,
* MDS/MPD overlap,
* ALL in CR;
* Multiple myeloma;
* CLL;
* Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
* Hodgkin's disease with chemosensitive disease or responding to checkpoint inhibitors.
\* Clinical situations
• Theoretical indication for a standard allo-transplant, but not feasible because:
* Age \> 50 yrs;
* Unacceptable end organ performance;
* The physician's decision;
* The patient's decision
* Underlying 'lower risk' disease, for which Reduced Intensity Conditioning is preferred (eg CLL, MCL)
\* Other inclusion criteria
* Male or female; fertile patients must use a reliable contraception method;
* Age 18-75 yrs (children of any age are not allowed in the protocol);
* Informed consent given by patient or his/her guardian if indicated.
Donors
* Male or female;
* Any age;
* Human Leukocyte Antigen (HLA)-identical sibling donor or 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA allele matched unrelated donor;
* Weight \> 15 Kg (because of leukapheresis);
* Fulfills criteria for allogeneic Peripheral Blood Stem Cell (PBSC) donation according to standard procedures;
* Informed consent given by donor or his/her guardian if indicated, as per donor center standard procedures.
Exclusion Criteria:
Patients
* Any condition not fulfilling inclusion criteria;
* Human Immunodeficiency Virus positive;
* Non-hematological malignancy(ies) (except non-melanoma skin cancer) active \< 3 years before Hematopoietic Cell Transplantation (HCT).
* Life expectancy severely limited by disease other than malignancy;
* Central Nervous System involvement with disease refractory to intrathecal chemotherapy.
* Terminal organ failure, except for renal failure (dialysis acceptable)
1. Cardiac: Symptomatic coronary artery disease; ejection fraction \<40%; uncontrolled arrhythmia, uncontrolled hypertension;
2. Pulmonary: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)\< 40% and/or receiving supplementary continuous oxygen, Forced Expiratory Volume in 1 Second (FEV1)\< 40%;
3. Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \>3 mg/dL, and symptomatic biliary disease;
* Uncontrolled infection;
* Karnofsky Performance Score \<70%;
* Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment;
* Patient is a female who is pregnant or breastfeeding;
* Any condition precluding the use of melphalan or Thymoglobulin;
Donors
* Any condition not fulfilling inclusion criteria;
* Unable to undergo leukapheresis because of poor vein access or other reasons.
Where this trial is running
Antwerp and 9 other locations
- ZNA Stuivenberg — Antwerp, Belgium (Recruiting)
- AZ Sint Jan Brugge — Bruges, Belgium (Recruiting)
- IJ Bordet — Brussels, Belgium (Recruiting)
- UZ Brussel — Brussels, Belgium (Recruiting)
- UCL St Luc — Brussels, Belgium (Recruiting)
- UZ Gent — Ghent, Belgium (Recruiting)
- UZ Leuven — Leuven, Belgium (Recruiting)
- CHU de Liège — Liège, Belgium (Recruiting)
- AZ Delta Roeselare — Roeselare, Belgium (Recruiting)
- CHU UCL Namur Godinne — Yvoir, Belgium (Recruiting)
Study contacts
- Principal investigator: Frédéric Baron, MD,Ph — Centre Hospitalier Universitaire de Liege
- Study coordinator: Frédéric Baron, MD,Ph
- Email: F.Baron@uliege.be
- Phone: +32 4 366 72 01
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.