Haploid Allogeneic Transplant Using the CliniMACS System

A Feasibility Study Evaluating Haploidentical Allogeneic Transplantation Using the CliniMACS System in Patients With Advanced Hematologic Malignancies

To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after transplantation.

Study Overview

• Status: Terminated
• Conditions: Acute Myelogenous Leukemia (AML) - Relapsed, Primary Refractory Disease or Poor Risk Factors; Chronic Myelogenous Leukemia (CML) - Accelerated or Second Chronic Phase; Myelodysplastic Syndrome (MDS) - High and Intermediate Risk; Non-Hodgkin's Lymphoma (NHL); Chronic Lymphocytic Leukemia (CLL) - Refractory
• Intervention / Treatment: Device: CliniMACS System

Detailed Description

To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant; assess the incidence of acute GvHD during the first 100 days after transplantation; and assess platelet engraftment, graft failure, chronic GvHD, clinical safety, and devise performance.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

RECIPIENT INCLUSION CRITERIA

Histopathologically-confirmed diagnosis of hematological or lymphatic malignancy, defined as one of the following:

• Acute myeloid leukemia (AML) as primary refractory disease, or in relapse
• Acute leukemia in first remission with poor risk factors and molecular prognosis
• AML with -5,-7, t(6;9), tri8, -11
• Acute lymphocytic / lymphoblastic leukemia (ALL) with Phil+ t(9;22),(q34;q11.2), and t(4:11)(q21;23)
• Chronic myelogenous leukemia (CML in accelerated, second chronic phase
• Myelodysplastic syndrome with high intermediate to high risk categories
• Non-Hodgkin's lymphoma (NHL)
• Chronic lymphocytic leukemia (CLL), Refractory < 50 years old at time of registration Donor is related Donor is genotypically-matched and haploidentical for HLA-A, B,C and DRB1, DQ loci Donor differs for 2 or 3 HLA alleles on the unshared haplotype in the GvHD direction No HLA-matched sibling or matched unrelated donor is identified ECOG performance status not more than 2 LVEF > 45% DLCO > 50% corrected for hemoglobin Serum creatinine
• < 1.5 mg/dL OR
• creatinine clearance > 50 mL/min for those above serum creatinine of 1.5 mg/dL serum bilirubin < 2.0 mg/dL ALT < 2x ULN (unless secondary to disease) Females of childbearing potential must have a negative serum or urine beta-HCG test within 3 weeks of registration No prior cancer within 5 years with the exception of surgically-cured, non-melanoma skin cancer or in situ cancer of the cervix No prior myeloablative therapy or transplant Duly-executed informed consent

RECIPIENT EXCLUSION CRITERIA Suitable candidate for autologous transplantation Participation in other investigational drugs or devices trials that might influence the study endpoints Evidence of active hepatitis Evidence of active cirrhosis HIV-positive History of invasive aspergillosis Presence of any other uncontrolled, active infection, ie, bacterial, viral or fungal Uncontrolled CNS involvement Documented allergy to murine proteins Documented allergy to iron dextran Lactating female Female of child-bearing potential unwilling to implement adequate birth control Medical problem / neurologic/psychiatric dysfunction which would impair his/her ability to be compliant with the medical regimen and/or to tolerate transplantation, in the opinion of the principal investigator Medical problem / neurologic/psychiatric dysfunction which would prolong hematologic recovery and place the recipient at unacceptable risk, in the opinion of the principal investigator would .

DONOR INCLUSION CRITERIA Age < 60 years Weight > 25 kg Medical history and physical examination confirm good health status as defined by institutional standards Within 30 days of apheresis collection, seronegative for HIV assessed as HIV Ag; HIV 1+2 Ab; or HTLV I/II Ab Within 30 days of apheresis collection, seronegative for hepatitis assessed as HBsAg; HBcAb (IgM and IgG); or HCV Ab Within 30 days of apheresis collection, seronegative for syphilis assessed as RPR Genotypically haploidentical as determined by HLA typing Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within 3 weeks of mobilization Capable of undergoing leukapheresis Has adequate venous access Willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate Agreeable to second donation of PBPC (or a bone marrow harvest) should the recipient fail to demonstrate sustained engraftment following the transplant Duly-executed informed consent Screened for CMV seroreactivity

• Must be seronegative donor if recipeint is seronegative.
• Otherwise the donor will be selected on the ability of NK cell alloreactivity based upon HLA typing results and donors who are capable of NK cell alloreactivity will be used preferentially.

DONOR EXCLUSION CRITERIA Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) Evidence of hepatitis (on screening) Medical, physical or psychological reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis Factors placing donor at increased risk for leukapheresis or G-CSF-related complications Lactating female Female of child-bearing potential unwilling to implement adequate birth control HIV-positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Haploidentical Allogeneic Transplant Using CliniMACS System; The CliniMACS cell selection system (Miltenyi Biotec) will be used to enrich hematopoietic stem cells from related, haploidentical, HLA-matched donors, who matched on the A,B,C and DRB1, DQ loci.

Device: CliniMACS System; The CliniMACS System is a cell selection device consisting of the following components: Computer-controlled instrument;; Sterile disposable tubing set (PVC tubing, filters and bags connected to two separation columns containing an iron/plastic matrix); Anti-CD34 antibody reagent (murine monoclonal antibody chemically coupled to a magnetic particle); Wash buffer; Other Names: CliniMACS Cell Selection System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Engraftment	Number of subjects recovering neutrophils, assessed as 1st of 3 consecutive days on which ANC > 0.5x10e9/L	30 days post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute GvHD (Grade II-IV)	Number of subjects with acute GvHD (grade II-IV) within 100 days post-transplant, per the Consensus Conference on Acute GvHD Grading (Przepiorka D, et al. Bone Marrow Transplantation. 1995. 15:825-828).	within 100 days post-transplant
Platelet Recovery	Number of subjects recovering platelets to > 20x10e9/L, assessed on the 7th day unsupported by platelet transfusions	40 days

Collaborators and Investigators

• Sponsor: Ginna Laport
• Investigators: Principal Investigator: Ginna G Laport, MD, Stanford Cancer Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): March 9, 2015
• Last Update Submitted That Met QC Criteria: February 26, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Precancerous Conditions; Leukemia, Lymphoid; Leukemia, B-Cell; Lymphoma; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Preleukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: IRB-12600; BMT123 (Other Identifier: OnCore); NCI-2011-00424 (Other Identifier: NCI PDQ); 77453 (Other Identifier: Historic IRB SQL database number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No