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

NCT00698685 | Terminated Phase 2 Results DMC

• 5 other identifiers: 05-0624-04R21CA10617705110UARIZ-05-0624-01UARIZ-SRC17920
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

Leukemia; Lymphoma; Hodgkin's Disease; Hematologic Neoplasms; Multiple Myeloma; Carcinoma, Renal Cell

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Actuarial Probability of Donor Hematopoietic Engraftment (Defined as at Least 50% Donor DNA in Bone Marrow at Day 100).

  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.

  Day 100 after transplant.

• Non-relapse Mortality at or Before Day 100

  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).

  Day 100 after transplant

Study Arms (1)

Preparative Regimen

EXPERIMENTAL

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.

Drug: Pentostatin; Biological: Alemtuzumab; Procedure: Allogeneic hematopoietic stem cell transplantation

Interventions

Pentostatin DRUG

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)

Also known as: Nipent

Preparative Regimen

Alemtuzumab BIOLOGICAL

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

Also known as: Campath

Preparative Regimen

Allogeneic hematopoietic stem cell transplantation PROCEDURE

Infusion of related or unrelated donor peripheral blood progenitor cells on day 0.

Also known as: HSCT

Preparative Regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Arizona Cancer Center at UMC North/University Medical Center

Tucson, Arizona, 85724, United States

Location

Arizona Cancer Center at UMC North

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Hodgkin Disease; Hematologic Neoplasms; Multiple Myeloma; Carcinoma, Renal Cell; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes

Interventions

Pentostatin; Alemtuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

We did not meet criteria to stop the study because of nonrelapse mortality (safety endpoint). However, we stopped accrual to the study because of failure to meet minimal criteria for engraftment (efficacy endpoint).

Results Point of Contact

• Title: Andrew M. Yeager, MD
• Organization: University of Arizona, Arizona Cancer Center

ayeager@azcc.arizona.edu

520-626-0662

Study Officials

• Andrew M Yeager, MD

  University of Arizona

  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 14, 2008
• First Posted: June 17, 2008
• Study Start: January 23, 2006
• Primary Completion: April 13, 2009
• Study Completion: April 26, 2011
• Last Updated: March 31, 2017
• Results First Posted: January 12, 2011

Record last verified: 2017-03

Locations

US (2)