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

This study has been terminated.
(Data indicate pentostatin/alemtuzumab regimen assocciated w/greater risk of graft failure when compared w/standard-reduced intensity regimen.)
Sponsor:
Collaborator:
Information provided by:
University of Arizona
ClinicalTrials.gov Identifier:
NCT00698685
First received: June 14, 2008
Last updated: March 16, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Hodgkin's Disease
Hematologic Neoplasms
Multiple Myeloma
Carcinoma, Renal Cell
Drug: Pentostatin
Biological: Alemtuzumab
Procedure: Allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Related or Unrelated Allogeneic Hematopoietic Cell Transplantation for High-Risk Malignancies, Using a Preparative Regimen of Pentostatin (Nipent®) and Alemtuzumab (Campath®)

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 14
Study Start Date: November 2005
Study Completion Date: November 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

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 infusion of related or unrelated donor peripheral blood progenitor cells 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.

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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00698685

Locations
United States, Arizona
Arizona Cancer Center at UMC North/University Medical Center
Tucson, Arizona, United States, 85724
Arizona Cancer Center at UMC North
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Andrew M Yeager, MD University of Arizona
  More Information

No publications provided

Responsible Party: Andrew M. Yeager, MD, Arizona Cancer Center/University Medical Center
ClinicalTrials.gov Identifier: NCT00698685     History of Changes
Obsolete Identifiers: NCT00543283
Other Study ID Numbers: 05-0624-04, NIH grant no. R21 CA106177, 05110, UARIZ-05-0624-01, UARIZ-SRC17920, P30CA023074
Study First Received: June 14, 2008
Results First Received: December 28, 2010
Last Updated: March 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
Allogeneic Hematopoietic Cell Transplantation
Preparative Regimen
Pentostatin
Alemtuzumab
Hodgkin Disease and Lymphoma, non-Hodgkin
leukemia, myeloid, acute
leukemia, lymphocytic, acute
leukemia, myeloid, chronic
leukemia, lymphocytic, chronic
Multiple Myeloma
Myelodysplastic Syndromes
Carcinoma, Renal Cell

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Carcinoma, Renal Cell
Hodgkin Disease
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Alemtuzumab

ClinicalTrials.gov processed this record on August 28, 2014