Phase II Trial of Pentostatin and Targeted Busulfan (Pento & tBU)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00496340
First received: June 29, 2007
Last updated: May 30, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Hematologic Malignancies
Drug: Pentostatin
Drug: Busulfan
Drug: Rituximab
Procedure: Allogeneic Hematopoietic Cell Transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Pentostatin and Targeted Busulfan as a Novel Reduced Intensity Regimen for Allogeneic Hematopoietic Stem Cell Transplantation Using Laboratory-Guided (CD4-guided) Immunosuppression.

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Incidence of Greater Than or Equal to 50% Donor Chimerism [ Time Frame: 28 days post-transplant ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Cumulative Incidence of Hematopoietic Cell Engraftment [ Time Frame: 28 days post-transplant ] [ Designated as safety issue: Yes ]
    Hematologic engraftment: defined as time to achieve an absolute neutrophil count (ANC) >/= 500/µl for 3 consecutive days or a platelet count of >/= 20,000//µl without the need for platelet support.

  • Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +28 [ Time Frame: 28 days post-transplant ] [ Designated as safety issue: Yes ]
    Median Percentage of Donor Cells in Study Population (Chimerism).

  • Rate of T-cell (CD3+) and Myeloid (CD33+) Chimerism by Day +100 [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: Yes ]
    Median Percentage of Donor Cells in Study Population (Chimerism).

  • Non-relapse Mortality Rate (NRM) [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: No ]
    The cumulative incidence of NRM after allo-HCT.

  • Incidence of Infections [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: Yes ]
    Infections: Incidence of infections (opportunistic and non-opportunistic) following conditioning.

  • Time to Incidence of Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: Yes ]

    The median time from allo-HCT to the initiation of tacrolimus (TAC) taper.

    The median time to onset of acute GVHD (aGVHD). Clinical manifestations of acute GVHD include a classic maculopapular rash; persistent nausea and/or emesis; abdominal cramps with diarrhea; and a rising serum bilirubin concentration.


  • Incidence of Graft Versus Host Disease (GVHD) [ Time Frame: Up to 2 years post-transplant ] [ Designated as safety issue: Yes ]

    By day +100, the cumulative incidence of GVHD, acute of grades 2-4, and 3-4.

    At 2 years, the cumulative incidence of chronic GVHD of any severity according to National Institutes of Health (NIH) consensus criteria. Diagnosis of chronic GVHD requires the presence of at least one diagnostic clinical sign of chronic GVHD or the presence of at least one distinctive manifestation confirmed by pertinent biopsy or other relevant tests in the same or another organ. Furthermore, other possible diagnoses for clinical symptoms must be excluded. No time limit is set for the diagnosis of chronic GVHD.

    At 2 years, the cumulative incidence of moderate/severe chronic GVHD.


  • Percentage of Participants With Progression Free Survival (PFS) [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    PFS at 2 years post-transplant. PFS, defined as time from day of hematopoietic cell infusion to disease relapse. Relapsed disease: Disease was in complete remission post-transplant but returned (e.g., >5% blast in bone marrow or any peripheral blasts).

  • Percentage of Participants With Overall Survival (OS) [ Time Frame: 2 years post-transplant ] [ Designated as safety issue: No ]
    OS at 2 years post-transplant. OS, defined as time from day of hematopoietic cell infusion to death from any cause.


Enrollment: 42
Study Start Date: July 2007
Study Completion Date: August 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:

  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

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.

Other Name: deoxycoformycin
Drug: Busulfan

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.

Other Names:
  • BU
  • Busulfex
Drug: Rituximab

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.

Other Name: Rituxan
Procedure: Allogeneic Hematopoietic Cell Transplant
Hematopoietic progenitor cells to be infused at least 36 hours after last dose of Busulfan.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496340

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Principal Investigator: Marcie Riches, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00496340     History of Changes
Other Study ID Numbers: MCC-15009
Study First Received: June 29, 2007
Results First Received: March 27, 2014
Last Updated: May 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Pentostatin
Busulfan
Rituxan
Allogeneic Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:
Rituximab
Busulfan
Pentostatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Adenosine Deaminase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014