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

This study is ongoing, but not recruiting participants.
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: January 16, 2013
Last verified: January 2013
History of Changes
  Purpose

The objective of this trial is to determine whether a regimen of pentostatin and busulfan (IV) can facilitate engraftment of 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/busulfan/rituximab/allogeneic hematopoietic cell transplant
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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:

MedlinePlus related topics: Cancer
U.S. FDA Resources

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

Primary Outcome Measures:
  • Achievement of greater than or equal to 50% donor chimerism by day +28 (chimerism studies (VNTR or STR) in CD3+ blood lymphocytes). [ Time Frame: CD33 chimerism by day +28 and +100, CD3 chimerism by day +100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of death from day of transplantation to day 100 from infusion with no evidence of persistent or relapsed disease. Incidence of death from day of transplantation to day 365 from infusion with no evidence of persistent or relapsed disease. [ Time Frame: 100 days, 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 41
Study Start Date: July 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Pentostatin/busulfan/rituximab/allogeneic hematopoietic cell transplant
 Drug: Pentostatin/busulfan/rituximab/allogeneic hematopoietic cell transplant

Pre-conditioning therapy:

All patients will receive pentostatin 4 mg/m2 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/m2 on day -4.
  3. Patient will then receive pentostatin at a dose of 4 mg/m2 by intravenous infusion over 1-2 hrs 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/m2 according to prescribing and institutional guidelines.

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  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 yrs 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.
  • ECOG performance status 0 - 1, or Karnofsky performance status of greater than 70

  • Organ function:

    1. Pulmonary: 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 pentostastin 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 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 NAT
  • Active CNS malignancy
  • Active infection
  • Unfavorable psychosocial evaluation or history of poor compliance to prescribed medical care.
  • Current use of metronidazole or acetominophen; 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
  • 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
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 Tomblyn, MD H. Lee Moffitt Cnacer Center & Research Center
  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: MCC15009
Study First Received: June 29, 2007
Last Updated: January 16, 2013
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on May 23, 2013