Phase 2
Completed N=42
Phase II Trial of Pentostatin and Targeted Busulfan
Source: ClinicalTrials.gov NCT00496340 ↗Enrolled (actual)
42
Serious AEs
59.5%
Results posted
Jun 2014
Primary outcomePrimary: Incidence of Greater Than or Equal to 50% Donor Chimerism — 100 percentage of participants
Summary
The objective of this trial is to determine whether a regimen of pentostatin and busulfan (IV) can facilitate engraftment of human leukocyte antigen (HLA) partially compatible siblings and unrelated donor transplants by using CD4+ laboratory-guided immunosuppression among 41 transplant patients meeting the inclusion criteria.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Greater Than or Equal to 50% Donor Chimerism |
100 | — |
| SECONDARY Cumulative Incidence of Hematopoietic Cell Engraftment |
97.6 | — |
| SECONDARY Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +28 |
87; 100 | — |
| SECONDARY Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +100 |
96; 100 | — |
| SECONDARY Non-relapse Mortality Rate (NRM) |
2; 17 | — |
| SECONDARY Incidence of Infections |
17; 3; 1; 5; 2 | — |
| SECONDARY Time to Incidence of Graft Versus Host Disease (GVHD) |
62; 33 | — |
| SECONDARY Incidence of Graft Versus Host Disease (GVHD) |
59; 19; 69; 58 | — |
| SECONDARY Percentage of Participants With Progression Free Survival (PFS) |
55 | — |
| SECONDARY Percentage of Participants With Overall Survival (OS) |
68 | — |
Eligibility Criteria
Inclusion Criteria
Recipients:
- Age: greater than 18 years of age, or younger with parental consent.
- HLA A, B, C, DRB1, DQB1, 10/10 or 9/10 allele sequence matched related donor or unrelated donor available
- Histologically confirmed diagnosis by pathologic review.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1, or Karnofsky performance status of greater than 70
- Organ function:
- Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) >/= 50%
- Cardiac: left ventricular ejection fraction >/= 50%
- Renal: creatinine clearance (measured or calculated) equal or greater than 50 ml/min (at any time pentostatin is administered)
- Hepatic: total bilirubin less than or equal to 2mg/dL, (Gilbert and other syndromes with increased indirect bilirubin should be allowed); serum transaminases less than two times the institutional upper limit of normal ( 18
- Signed informed consent form in accordance with institutional or National Donor Marrow Program (NMDP) policies
Exclusion Criteria
Recipients:
- Pregnant or lactating women
- HIV or seropositive, confirmed by nucleic acid test (NAT)
- Active central nervous system (CNS) malignancy
- Active infection
- Unfavorable psychosocial evaluation or history of poor compliance to prescribed medical care.
- Current use of metronidazole or acetaminophen; patients must discontinue use of these agents at least 7 days prior to the start of Busulfex administration
- Prior allogeneic HCT (patients who had received a prior autologous HCT will be allowed)
- Lack of a capable caregiver.
- Presence of any of the following comorbid conditions
- History of recent myocardial infarction within 30 days
- Congestive heart failure (NY class III, IV or if symptomatically uncontrolled)
- Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency)
- Untreated thoracic or abdominal aneurysm (6 cm or more)
- History of any cerebrovascular accident including transient ischemic attacks within 30 days
- Dementia
- History of recent gastrointestinal bleeding (within 30 days)
- Connective tissue/rheumatologic disorders
- Hemiplegia/paraplegia
- History of solid tumor excluding skin or cervical carcinoma after curative resection. Patients with other prior solid tumor (s) who are in remission for more than 5 years will be allowed on a case-by-case basis
Donors:
- Pregnant or lactating women
- HIV seropositive, confirmed by NAT
- Human T- lymphotropic virus (HTLV) I/II seropositive
- Hepatitis B or C seropositive
- Donors with uncontrolled bacterial, viral, fungal or parasitic infections.
- Donors with known hypersensitivity to recombinant human G-CSF or any E. coli-derived products.
Data sourced from ClinicalTrials.gov (NCT00496340). 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. Informational only — not medical advice.