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Methods to Enhance the Safety and Effectiveness of Stem Cell Transplants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Minoo Battiwalla, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00378534
First received: September 19, 2006
Last updated: December 22, 2014
Last verified: December 2014
  Purpose

Bone marrow stem cell transplants (otherwise called bone marrow transplants) from healthy donors are sometimes the only means of curing hematological malignant diseases such as acute and chronic leukemias, myelodysplastic syndrome, myeloproliferative diseases and lymphomas. Before transplant the patient receives chemotherapy and radiation treatment to reduce the malignancy to low levels and to prevent rejection of the transplant. The transplant restores the blood counts to normal and replaces the patients immunity with that of the donor. The donor's immune cells increase the effect of the transplant by attacking remaining malignant cells. Donor immune cells (especially those called T lymphocytes) also attack healthy non-cancerous cells and tissues of the recipient causing "graft-versus-host-disease" (GVHD). Strong GVHD reactions occurring within weeks after the transplant can be life-threatening . In this study we remove most of the T lymphocytes from the transplant to minimize the risk of GVHD. However to improve immunity against residual malignant cells and boost immunity to infections, donor T cells (stored frozen at time of transplant) are given back around 90 days after the transplant when they have a reduced risk of causing serious GVHD.

Any patient between 10 and 75 years of age with acute or chronic leukemia, myelodysplastic syndrome, myeloproliferative syndromes or lymphoma, who have a family member who is a suitable stem cell donor may be eligible for this study. Candidates are screened with a medical history and various tests and examinations.


Condition Intervention Phase
Chronic Myelogenous Leukemia
Acute Myelogenous Leukemia
Chronic Lymphocytic Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Device: Miltenyi reagent system
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: Peripheral Blood Stem Cell Allotransplantation for Hematological Malignancies Using a Positive Stem Cell Selection Technique for T Cell Depletion, Followed by Delayed T Cell Add-Back

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Survival and Non-relapse Mortality at Day +200 Using the Miltenyi Reagent System [ Time Frame: Day 200 ] [ Designated as safety issue: Yes ]
    Subjects with hematological malignancies receiving a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infucion at day 90. The subjects receiveing allogeneic stem cell transplantation will have stem cell product prepared using Miltenyi CliniMacs system to determine the overall survival and non-relapse mortality at day +200.


Secondary Outcome Measures:
  • Standard Transplant Outcome Variables Such as Non-hematologic Toxicity, Incidence and Severity of Acute and Chronic GVHD and Relapse of Disease. [ Time Frame: 3 years maximum ] [ Designated as safety issue: Yes ]

Enrollment: 115
Study Start Date: September 2006
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Miltenyi reagent system

The protocol will evaluate survival at day +200 in subjects with hematological malignancies receiving myeloablative conditioning regimen of cyclophosphamidem fludarabine and total body irradiation followed by an infusion of a stem cell prodict prepared using the Miltenyi CliniMacs system for CD34 selection and a delayed T cell depletion add back as donor lymphocyte infusion (DLI) at day 90.

The objective is to determine the overall survival rate at day +200 following allogeneic peripheral blood stem cell allotransplantation (PBSCT)

Device: Miltenyi reagent system
Miltenyi Clinimax CD34 Reagent System for CD34 selectioni and delayed T cell depletion add back
Other Name: Miltenyi Clinimax CD34 Reagent System

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   10 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA - RECIPIENT:

  • Ages 10-75 years inclusive
  • Chronic myelogenous leukemia (CML):
  • Subjects under the age of 21 in chronic phase
  • Subjects ages 10-75 in chronic phase who have failed treatment with imatinib, have intolerance to imatinib, or who did not receive imatinib at therapeutic doses within the first 12 months from diagnosis.
  • Subjects ages 10-75 in accelerated phase or blast transformation.
  • Acute lymphoblastic leukemia (ALL): any of these categories: ALL in first remission with high-risk features (presenting leukocyte count greater than 100,000/cu mm, Karyotypes t9; 22, t4, t19, t11, biphenotypic leukemia) All second or subsequent remissions, primary induction failure, partially responding or untreated relapse.
  • Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse
  • Myelodysplastic syndromes (MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes
  • Myeloproliferative disorders including atypical (Ph negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia.
  • Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /microl) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy.
  • Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments
  • Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments.
  • HLA identical (6/6) related donor
  • For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: written informed consent from one parent or guardian. Informed oral consent from minors: the process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA - RECIPIENT: (ANY OF THE FOLLOWING)

  • Estimated probability of surviving less than three months
  • Major anticipated illness or organ failure incompatible with survival from transplant
  • Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
  • Positive pregnancy test for women of childbearing age.
  • HIV positive
  • DLCO adjusted for ventilation and hemoglobin less than 65 percent predicted
  • Left ventricular ejection fraction less than 40 percent
  • AST/SGOT greater than 10 times ULN (CTCAE grade IV v3.0)
  • Bilirubin greater than 5 times ULN (CTCAE grade IV v3.0)
  • Creatinine greater than 4.5 times ULN (CTCAE grade IV v 3.0)
  • Prior allogeneic stem cell transplantation.

INCLUSION CRITERIA - DONOR:

  • Related donor, HLA identical (6/6) with recipient
  • Weight greater than or equal to 18 kg
  • Age greater than or equal to 2 or less than or equal to 80 years old
  • For adults: Ability to comprehend the investigational nature of the study and provide informed consent. For minors: Written informed consent from one parent or guardian and informed assent: The process will be explained to the minor on a level of complexity appropriate for their age and ability to comprehend.

EXCLUSION CRITERIA - DONOR: (ANY OF THE FOLLOWING)

  • Pregnant. Lactating donors permitted provide breast milk is discarded during the days that G-CSF is given
  • Unfit to receive filgrastim (G-CSF) and undergo apheresis (abnormal blood counts, history of stroke, uncontrolled hypertension)
  • Sickling hemoglobinopathies including HbSS, HbAS, HbSC
  • HIV positive donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II) will be used at the discretion of the investigator following counseling and approval from the recipient
  • Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible
  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: NCT00378534

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Minocher M Battiwalla, M.D. National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Minoo Battiwalla, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00378534     History of Changes
Obsolete Identifiers: NCT00398346
Other Study ID Numbers: 060248, 06-H-0248
Study First Received: September 19, 2006
Results First Received: December 22, 2014
Last Updated: December 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Chronic Myelogenous Leukemia (CML)
Acute Myelogenous Leukemia (AML)
Chronic Lymphocytic Leukemia (CLL)
Acute Lymphoblastic Leukemia (ALL)
Myelodysplastic Syndrome (MDS)
Leukemia
Chronic Myelogenous Leukemia
CML
Acute Myeloid Leukemia
AML
Chronic Lymphocytic Leukemia
CLL
Acute Lymphoblastic Leukemia
ALL
Myelodysplasia Syndrome

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on March 02, 2015