Fludarabine treatment for bone marrow failure syndromes
Fludarabine-Based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients With Bone Marrow Failure Syndromes
This study is testing if a special treatment with fludarabine can help people with bone marrow failure syndromes do better after receiving a bone marrow transplant from a related donor.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 25 (estimated) |
| Ages | N/A to 22 Years |
| Sex | All |
| Sponsor | Children's Hospital of Philadelphia Academic / other |
| Drugs / interventions | fludarabine, cyclophosphamide |
| Locations | 1 site (Philadelphia, Pennsylvania) |
| Trial ID | NCT02928991 on ClinicalTrials.gov |
What this trial studies
This pilot study evaluates the effectiveness of fludarabine-based reduced intensity conditioning (RIC) regimens in facilitating donor engraftment for patients with acquired aplastic anemia and inherited bone marrow failure syndromes undergoing matched related donor bone marrow transplant. Patients will receive a specific regimen based on their condition, and outcomes will be compared to historical data and published results. The study aims to assess donor chimerism and various clinical outcomes, including survival and graft failure, following the transplant.
Who should consider this trial
Good fit: Ideal candidates are patients aged 0-22 years with severe acquired aplastic anemia or diagnosed inherited bone marrow failure syndromes who have a fully HLA-matched related donor.
Not a fit: Patients who do not have a suitable related donor or those with conditions not meeting the eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could improve donor engraftment and overall outcomes for patients with severe bone marrow failure syndromes.
How similar studies have performed: Previous studies have shown promise with fludarabine-based regimens in similar patient populations, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Patients 0-22 years with acquired aplastic anemia or a diagnosed inherited bone marrow failure syndrome, and a fully Human leukocyte antigen (HLA)-matched (10/10) related donor.
Inclusion Criteria:
Patient:
1. Ages 0-22 years at time of enrollment
2. Diseases:
* Patients with severe or very severe acquired AA, defined by:
* Bone marrow biopsy demonstrating cellularity of \<25% (at least 2 weeks from last dose of G-CSF), in addition to 2 of the following: absolute neutrophil count (ANC) \<500/µL, platelets \< 20,000/µL and absolute reticulocytes \<40,000/µL
* Negative evaluation for inherited bone marrow failure conditions and negative evaluation for dysplasia or cytogenetic abnormalities associated with myelodysplastic syndromes
* Patients with concurrent paroxysmal nocturnal hemoglobinuria (PNH) clones are eligible, as long as they meet criteria for severe or very severe aplastic anemia as defined above
* Patients with clinically diagnosed and/or genetically proven iBMF syndromes, resulting in chronic red blood cell or platelet-transfusion dependence and/or an absolute neutrophil count \<500/µL. These disorders include, but are not limited to:
* Fanconi Anemia
* Dyskeratosis Congenita
* Severe Congenital Neutropenia
* Diamond-Blackfan Anemia
* Congenital Dyserythropoietic/Sideroblastic Anemias
* Congenital Amegakaryocytic Thrombocytopenia
* Shwachman-Diamond Syndrome
3. Lansky or Karnofsky performance \>60
4. HLA matched related donor available.
5. No active untreated infection
6. Females of childbearing potential must have negative pregnancy test.
Organ Function:
* Serum creatinine \<1.5xupper limit of normal for age Hepatic: Transaminases \<5x normal
* Cardiac shortening fraction \>27%
* Bilirubin \<2.5x normal (unless elevation due to Gilberts disease).
Donor Selection Criteria:
* Donor selection will comply with U.S. Food and Drug Administration's Code of Federal Regulations
* Fully HLA-matched related donor.
* Donor must be at least 6 months of age
* Donor suitable for bone marrow collection and meets eligibility for donation, including fulfilling infectious disease criteria as per SOP, including HIV, Hepatitis B, Hepatitis C Polymerase chain reaction (PCR) negative.
* If subject has confirmed iBMF syndrome, donor must be evaluated for this disorder and testing must be negative
* Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
* Donor evaluation and collection procedure as per CHOP Standard Operating Procedures (SOP)
Exclusion Criteria:
* Uncontrolled bacterial, viral or fungal infections
* HLA matched related donor unable to donate bone marrow.
* No eligible fully HLA-matched related donor
* Pregnant females
* Patients with a clinical diagnosis of Myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
* Patients with PNH without underlying bone marrow aplasia
Where this trial is running
Philadelphia, Pennsylvania
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Principal investigator: Timothy Olson, MD, PhD — Children's Hospital of Philadelphia
- Study coordinator: Megan Atkinson
- Email: cttsbmtintake@chop.edu
- Phone: 215-590-2820
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.