Phase II Trial of Pentostatin and Targeted Busulfan

NCT00496340 | Completed Phase 2 Results

• 1 other identifier: MCC-15009
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematologic Malignancies

Keywords

Pentostatin; Busulfan; Rituxan; Allogeneic Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Incidence of Greater Than or Equal to 50% Donor Chimerism

  The primary endpoint was achievement of \>/= 50% donor chimerism in CD3+ peripheral blood lymphocytes by day +28 (± 7) after allogeneic hematopoietic cell transplantation (allo-HCT).

  28 days post-transplant

Secondary Outcomes (9)

• Cumulative Incidence of Hematopoietic Cell Engraftment

  28 days post-transplant

• Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +28

  28 days post-transplant

• Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +100

  100 days post-transplant

• Non-relapse Mortality Rate (NRM)

  Up to 2 years post-transplant

• Incidence of Infections

  Up to 2 years post-transplant

Study Arms (1)

Conditioning Followed by HCT

EXPERIMENTAL

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: 1. Patients will receive anti-seizure prophylaxis with lorazepam 0.5 mg every 6 hours beginning day -6. 2. Intravenous Busulfan (1st dose) at a dose of 200mg/m\^2 on day -4. 3. Patient will then receive pentostatin at a dose of 4 mg/m\^2 by intravenous infusion over 1-2 hours on days -4, -3. 4. Intravenous Busulfan (2nd dose) will be administered on day (-2) to target a total AUC of 16,000 +/- 1600. 5. Hematopoietic progenitor cells to be infused at least 36 hours after last dose of Busulfan. 6. 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.

Drug: Pentostatin; Drug: Busulfan; Drug: Rituximab; Procedure: Allogeneic Hematopoietic Cell Transplant

Interventions

Pentostatin DRUG

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.

Also known as: deoxycoformycin

Conditioning Followed by HCT

Busulfan DRUG

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.

Also known as: BU, Busulfex

Conditioning Followed by HCT

Rituximab DRUG

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.

Also known as: Rituxan

Conditioning Followed by HCT

Allogeneic Hematopoietic Cell Transplant PROCEDURE

Hematopoietic progenitor cells to be infused at least 36 hours after last dose of Busulfan.

Conditioning Followed by HCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Pentostatin; Busulfan; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Bone marrow chimerism data were available for only 38 patients at day +28 and for only 36 patients at day +100.

Results Point of Contact

• Title: Marcie Riches, MD
• Organization: H. Lee Moffitt Cancer Center and Research Institute

marcie.riches@moffitt.org

813-745-6284

Study Officials

• Marcie Riches, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2007
• First Posted: July 4, 2007
• Study Start: July 1, 2007
• Primary Completion: April 1, 2013
• Study Completion: August 1, 2013
• Last Updated: June 5, 2014
• Results First Posted: June 5, 2014

Record last verified: 2014-03

Locations

US (1)