Phase 2
N=80
HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide
Myelodysplastic Syndrome (MDS) · Chronic Lymphocytic Leukemia (CLL) · Chemotherapy-sensitive Lymphoma · Acute Lymphoblastic Leukemia (ALL)/T Lymphoblastic Lymphoma · Acute Myelogenous Leukemia (AML)
Bottom Line
View on ClinicalTrials.gov: NCT02793544 ↗Enrolled (actual)
80
Serious AEs
31.3%
Results posted
Aug 2025
Primary outcome: Primary: Overall Survival — 72.3; 78.9 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Fludarabine (Drug); Cyclophosphamide 14.5 mg/kg/day IV on Days -6, -5 (Drug); Total Body Irradiation (TBI) 200cGy on Day -1 (Radiation); Infusion of non-T-cell depleted bone marrow on Day 0 (Procedure); Busulfan (Drug); Cyclophosphamide 50mg/kg/day IV on Days -2,-1 (Drug); Cyclophosphamide 50mg/kg/day IV on Days -5,-4 (Drug); Total Body Irradiation (TBI) 200cGy twice a day on Days -3, -2, -1 (Radiation); Post-HCT Cyclophosphamide 50mg/kg IV on Day+3, +4 (Drug); Sirolimus (Drug); Mycophenolate mofetil (Drug); G-CSF (Drug); Pre-HCT Mesna on Days -6 and -5 (Drug); Pre-HCT Mesna on Days -2 and -1 (Drug); Pre-HCT Mesna on Days -5 and -4 (Drug); Post-HCT Mesna (Drug)
- Age
- Pediatric, Adult, Older Adult · 15+ yrs
- Sex
- All
- Sponsor
- Center for International Blood and Marrow Transplant Research
- Primary completion
- Mar 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival |
72.3; 78.9 | — |
| SECONDARY Progression-free Survival |
69.9; 72.5; 62.1; 67.5 | — |
| SECONDARY Transplant-related Mortality |
5; 7.5; 7.5; 7.5; 7.5; 10 | — |
| SECONDARY Cumulative Incidence of Neutrophil Recovery |
97.5; 97.5; 97.5; 97.5 | — |
| SECONDARY Cumulative Incidence of Platelet Recovery |
87.5; 95; 90; 95 | — |
| SECONDARY Cumulative Incidence of Acute GVHD |
42.5; 32.5; 17.5; 0 | — |
| SECONDARY Grades II-IV Acute GVHD |
42.5; 32.5 | — |
| SECONDARY Grades III-IV Acute GVHD |
17.5; 0 | — |
| SECONDARY Cumulative Incidence of Chronic GVHD |
27.6; 10; 35.5; 17.5 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 CMV Reactivation or Infection |
10.4; 7.6; 10.4; 7.6; 10.4; 7.6 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 3 CMV Infection |
0; 2.6; 0; 2.6; 0; 2.6 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 EBV Infection |
0; 0; 2.9; 0; 2.9; 0 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 2 BK Virus Infection |
26.7; 29.7; 26.7; 29.7; 26.7; 29.7 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 2-3 Adenovirus Infection |
2.6; 0; 9; 9.4; 9; 12.6 | — |
| SECONDARY Cumulative Incidences of Viral Reactivations and Infections: Grade 2 HHV-6 Infection |
12.5; 5.1; 12.5; 5.1; 12.5; 5.1 | — |
| SECONDARY Cumulative Incidence of Relapse/Progression |
22.6; 20; 30.4; 22.5 | — |
| SECONDARY Cumulative Incidences of Thrombotic Microangiopathy (TMA) and Hepatic Veno-occlusive Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) |
5; 0; 10; 2.5 | — |
| SECONDARY Cumulative Incidence of Primary Graft Failure |
0; 3 | — |
| SECONDARY Donor Chimerism |
100; 99.1; 100; 100; 100; 100 | — |
| SECONDARY Peripheral Blood Chimerism |
24; 27 | — |
| SECONDARY Proportion of Subjects Proceeding to Transplant |
80 | — |
| SECONDARY Time From Search to Donor Identification |
77.5; 88.5 | — |
| SECONDARY Donor Selection Characteristics: HLA Match |
26; 23; 49; 8; 11; 19 | — |
| SECONDARY Donor Selection Characteristics: Donor Age |
27; 29; 29 | — |
| SECONDARY Donor Selection Characteristics: Donor Age, Categorical |
24; 23; 47; 9; 11; 20 | — |
| SECONDARY Donor Selection Characteristics: Donor Weight |
77; 77; 77 | — |
| SECONDARY Donor Selection Characteristics: Donor Sex |
20; 24; 44; 20; 16; 36 | — |
| SECONDARY Donor Selection Characteristics: Donor and Recipient Sex |
12; 12; 24; 8; 12; 20 | — |
| SECONDARY Donor Selection Characteristics: Donor and Recipient CMV Serostatus |
18; 13; 31; 6; 5; 11 | — |
| SECONDARY Donor Selection Characteristics: Donor and Recipient ABO Blood Match |
20; 24; 44; 12; 5; 17 | — |
| SECONDARY Donor Clonal Hematopoiesis |
0; 0 | — |
| SECONDARY Subgroup Analysis of HIV-positive Subjects |
0; 1; 0; 2; 0; 1 | — |
Summary
This is a multi-center, single arm Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation donors and post-transplantation cyclophosphamide (PTCy), sirolimus and mycophenolate mofetil (MMF) for graft versus host disease (GVHD) prophylaxis in patients with hematologic malignancies.
Eligibility Criteria
Inclusion Criteria
- Age ≥ 15 years and 40 mL/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula for those aged ≥ 18 years; by Original Schwartz estimate for those 750 copies/mL should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the ARV review (described in Appendix D).
- May not be currently prescribed ritonavir, cobacistat and/or zidovudine
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
- Prior allogeneic HCT
- History of primary idiopathic myelofibrosis
- MDS subjects may not receive RIC and must be < 50 years of age at the time of signing the informed consent form
Data sourced from ClinicalTrials.gov (NCT02793544). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.