Phase II Trial of Pentostatin and Targeted Busulfan (Pento & tBU)
Hematologic Malignancies
About this trial
This is an interventional treatment trial for Hematologic Malignancies focused on measuring Pentostatin, Busulfan, Rituxan, Allogeneic Hematopoietic Stem Cell Transplantation
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 (< 2 x ULN).
Donors:
- Capable of receiving Granulocyte Colony-Stimulating Factor (G-CSF) and undergo apheresis
- Age >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.
Sites / Locations
- H. Lee Moffitt Cancer Center & Research Institute
Arms of the Study
Arm 1
Experimental
Conditioning Followed by HCT
Pentostatin/Busulfan/Rituximab/Allogeneic Hematopoietic Cell Transplant (HCT). Pre-conditioning therapy: All participants will receive pentostatin 4 mg/m^2 on day -28. Patients may receive additional doses on days -21 & -14 depending on cell counts. Conditioning: Patients will receive anti-seizure prophylaxis with lorazepam 0.5 mg every 6 hours beginning day -6. Intravenous Busulfan (1st dose) at a dose of 200mg/m^2 on day -4. Patient will then receive pentostatin at a dose of 4 mg/m^2 by intravenous infusion over 1-2 hours on days -4, -3. Intravenous Busulfan (2nd dose) will be administered on day (-2) to target a total AUC of 16,000 +/- 1600. Hematopoietic progenitor cells to be infused at least 36 hours after last dose of Busulfan. Rituximab: Patients with CD20+ expressing malignancies will be treated with rituximab at a dose of 375 mg/m^2 according to prescribing and institutional guidelines.