Phase II Trial of Pentostatin and Targeted Busulfan
Condition: Hematologic Malignancies
MeSH terms: Hematologic Neoplasms
Intervention: Pentostatin; Busulfan; Rituximab; Allogeneic Hematopoietic Cell Transplant
Intervention description: 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.
Participant will receive pentostatin at a dose of 4 mg/m^2 by intravenous infusion over 1-2 hours on days -4, -3.; Pre-conditioning therapy:
Intravenous Busulfan (1st dose) at a dose of 200mg/m^2 on day -4.
Intravenous Busulfan (2nd dose) will be administered on day (-2) to target a total AUC of 16,000 +/- 1600.; Pre-conditioning therapy:
Patients with CD20+ expressing malignancies will be treated with rituximab at a dose of 375 mg/m^2 according to prescribing and institutional guidelines.; Hematopoietic progenitor cells to be infused at least 36 hours after last dose of Busulfan.
Intervention MeSH terms: Rituximab; Busulfan; Pentostatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pentostatin; Busulfan; Rituxan; Allogeneic Hematopoietic Stem Cell Transplantation

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.
    

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:

               1. Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) >/= 50%

               2. Cardiac: left ventricular ejection fraction >/= 50%

               3. Renal: creatinine clearance (measured or calculated) equal or greater than 50
                  ml/min (at any time pentostatin is administered)

               4. 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

               1. History of recent myocardial infarction within 30 days

               2. Congestive heart failure (NY class III, IV or if symptomatically uncontrolled)

               3. Peripheral vascular disease (including intermittent claudication or history of
                  bypass for arterial insufficiency)

               4. Untreated thoracic or abdominal aneurysm (6 cm or more)

               5. History of any cerebrovascular accident including transient ischemic attacks
                  within 30 days

               6. Dementia

               7. History of recent gastrointestinal bleeding (within 30 days)

               8. Connective tissue/rheumatologic disorders

               9. Hemiplegia/paraplegia

              10. 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.