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Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT00698685
Recruitment Status : Terminated (Pentostatin/alemtuzumab regimen had greater risk of graft failure.)
First Posted : June 17, 2008
Results First Posted : January 12, 2011
Last Update Posted : March 31, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona

Tracking Information
First Submitted Date  ICMJE June 14, 2008
First Posted Date  ICMJE June 17, 2008
Results First Submitted Date  ICMJE December 28, 2010
Results First Posted Date  ICMJE January 12, 2011
Last Update Posted Date March 31, 2017
Actual Study Start Date  ICMJE January 23, 2006
Actual Primary Completion Date April 13, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2011)
  • Actuarial Probability of Donor Hematopoietic Engraftment (Defined as at Least 50% Donor DNA in Bone Marrow at Day 100). [ Time Frame: Day 100 after transplant. ]
    The number of participants with donor hematopoietic engraftment at day 100 is reported in the data table, and the actuarial probability is calculated using the Kaplan-Meier product-limit estimate statistic, as reported in the statistical analysis section below.
  • Non-relapse Mortality at or Before Day 100 [ Time Frame: Day 100 after transplant ]
    The primary safety outcome is indicated by the number of participants who died at or before Day 100 after transplant for any reason other than relapse of disease (Leukemia, Lymphoma, Hodgkin's disease, Hematologic Neoplasms, Multiple Myeloma, Renal Cell Carcinoma).
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2008)
  • Presence of donor lymphohematopoietic chimerism in peripheral blood by day 100 post-transplant
  • Non-relapse mortality at day 100 post-transplant
Change History Complete list of historical versions of study NCT00698685 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation
Official Title  ICMJE Phase II Related or Unrelated Allogeneic Hematopoietic Cell Transplantation for High-Risk Malignancies, Using a Preparative Regimen of Pentostatin (Nipent®) and Alemtuzumab (Campath®)
Brief Summary This study tests the hypothesis that a purely immunosuppressive preparative regimen allows engraftment of related or unrelated allogeneic hematopoietic stem cells in subjects with high-risk malignancies, without causing the post-transplant myelosuppression (e.g., neutropenia, thrombocytopenia) that occurs with currently used reduced-intensity (nonmyeloablative) preparative regimens. This study incorporates both safety and efficacy endpoints and evaluates a novel preparative regimen of alemtuzumab plus continuous-infusion pentostatin, two immunosuppressive agents with different mechanisms of action, in recipients of related or unrelated allogeneic hematopoietic stem cell transplantation.
Detailed Description

Primary Objectives of the study:

  • To determine the efficacy of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic peripheral blood stem cell transplantation (PBSCT) in inducing durable donor lymphohematopoietic cell chimerism (defined as at least 50% donor cells in the peripheral blood) by 100 days after PBSCT (day +100) in subjects with high-risk malignancies who are at high risk for morbidity and mortality with conventional intensive pre-transplant conditioning regimens.
  • To determine the safety of a preparative regimen of pentostatin and alemtuzumab plus related or unrelated allogeneic PBSCT, as measured by the non-relapse mortality at day +100 in the study subject population.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
  • Hodgkin's Disease
  • Hematologic Neoplasms
  • Multiple Myeloma
  • Carcinoma, Renal Cell
Intervention  ICMJE
  • Drug: Pentostatin
    Days - 8 through -6: pentostatin 4 mg/m2/24 hr as a continuous intravenous infusion (CIVI) (total cumulative dose, 12 mg/m2 over 3 days)
    Other Name: Nipent
  • Biological: Alemtuzumab
    Days - 5 through - 1: alemtuzumab 20 mg per dose intravenously over 8 hours daily for 5 doses (total cumulative dose, 100 mg)
    Other Name: Campath
  • Procedure: Allogeneic hematopoietic stem cell transplantation
    Infusion of related or unrelated donor peripheral blood progenitor cells on day 0.
    Other Name: HSCT
Study Arms  ICMJE Experimental: Preparative Regimen

Days - 8 through -6: pentostatin 4 mg/m2/24 hr as a continuous intravenous infusion (CIVI) (total cumulative dose, 12 mg/m2 over 3 days)

Days - 5 through - 1: alemtuzumab 20 mg per dose intravenously over 8 hours daily for 5 doses (total cumulative dose, 100 mg)

Followed by Allogeneic hematopoietic stem cell transplantation, related or unrelated donor, on day 0. Patients also receive cyclosporine intravenous (IV) continuously beginning on day -2, continuing (IV or orally) until day 100, followed by a taper.

Interventions:
  • Drug: Pentostatin
  • Biological: Alemtuzumab
  • Procedure: Allogeneic hematopoietic stem cell transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 23, 2010)
14
Original Enrollment  ICMJE
 (submitted: June 14, 2008)
115
Actual Study Completion Date  ICMJE April 26, 2011
Actual Primary Completion Date April 13, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

One of these diagnoses:

  • Acute myeloid leukemia in complete or partial remission
  • Acute lymphocytic leukemia in complete or partial remission
  • Chronic myeloid leukemia in first or subsequent chronic phase or accelerated phase
  • Chronic lymphocytic leukemia that has recurred or failed after at least one course of front-line therapy
  • Hodgkin's disease or non-Hodgkin's lymphoma that has failed front-line therapy, is in second or subsequent remission, or is in chemosensitive relapse
  • Multiple myeloma that is in complete or partial remission or in chemosensitive relapse
  • Myelodysplastic Syndrome classified as intermediate-2 or high risk according to International Prognostic Scoring System
  • Metastatic renal cell carcinoma that has failed at least one previous front-line chemotherapy and/or biological therapy regimen and that is radiographically detectable and evaluable
  • Treatment with at least one previous course of chemotherapy or biological therapy for the malignancy for which allogeneic PBPCT is being considered (i.e., a subject cannot be enrolled on this study for initial treatment of a malignancy).

AND at least one of the following:

  • Age 50 years or older.
  • Previous transplant with autologous or allogeneic hematopoietic cells (peripheral blood, bone marrow, or placental blood).
  • High-risk status of hematologic malignancy, i.e., not in first complete remission or first chronic phase.
  • Presence of other medical condition that could place subject at unacceptably high risk of regimen-related mortality such as documented chronic bronchitis or emphysema; decreased cardiac ejection fraction (but with ejection fraction at least 30%), or history of coronary artery disease; renal insufficiency (but with creatinine clearance at least 30 mL/min); hepatic cirrhosis (but with normal hepatic synthetic function); or documented or presumed invasive fungal infection requiring treatment with intravenous antifungal agent(s).

Exclusion Criteria:

  • Eligibility for another clinical therapeutic protocol or standard-of-care treatment that offers higher probability of cure or long-term control of subject's malignancy.
  • Progressive Hodgkin's disease, non-Hodgkin's lymphoma, Hodgkin disease or multiple myeloma that is refractory to salvage chemotherapy.
  • Acute leukemia (AML or ALL) in relapse, CML in blast phase/blast crisis, or MDS with greater than 30% marrow involvement (MDS-AML). Subjects with these disease characteristics may be considered for this study if complete or partial remissions (CRs or PRs) occur after salvage chemotherapy.
  • Severe organ dysfunction, such as: cardiac ejection fraction below 30% or symptomatic ischemic cardiac disease; creatinine clearance below 30 mL/min; carbon monoxide diffusing capacity (DLCO) below 35% and/or need for supplemental oxygen; severe hepatic cirrhosis with ascites and/or varices; hepatic dysfunction associated with abnormal synthetic function (e.g., coagulopathy) and/or bilirubin greater than two times upper limit of normal and/or transaminases (AST or ALT) above four times upper limit of normal.
  • Untreated or progressive central nervous system involvement by malignancy
  • Subject is pregnant or breast-feeding.
  • Karnofsky score below 50
  • Seropositivity for human immunodeficiency virus (HIV).
  • Life expectancy less than 12 weeks with conventional treatments.
  • For subjects who are fertile, refusal to practice contraception upon entering this study and for at least 12 months after PBPCT or after cessation of immunosuppressive treatments (e.g., cyclosporine), whichever occurs later.
  • Failure to obtain at least 5.0 x 106 allogeneic donor CD34+ cells per kg of recipient weight in PBPC product.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00698685
Other Study ID Numbers  ICMJE 05-0624-04
R21CA106177 ( U.S. NIH Grant/Contract )
05110 ( Other Identifier: University of Arizona )
UARIZ-05-0624-01 ( Other Identifier: University of Arizona )
UARIZ-SRC17920 ( Other Identifier: Arizona Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Arizona
Study Sponsor  ICMJE University of Arizona
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Andrew M Yeager, MD University of Arizona
PRS Account University of Arizona
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP