Allogeneic Transplantation From Related Haploidentical Donors

Sponsor
Stanford University (Other)
Overall Status
Completed
CT.gov ID
NCT00185692
Collaborator
(none)
16
Enrollment
1
Location
1
Arm
124
Duration (Months)
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

An alternative to conventional allogeneic bone marrow transplantation is by using a non-myeloablative conditioning regimen. This regime would consist of both; total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG). Used in combination to achieve engraftment of haploidentical CD34+ selected peripheral blood stem cells in older patients or patients with underlying medical conditions that preclude standard allogeneic treatment. The expected results of this transplant regime will be expected to result in hematopoietic and immunologic reconstitution, decreased deaths related to the treatment regimen and decreased gravft-vs-host disease (GVHD).

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Allogeneic Hematopoietic Cell Transplantation of Positively Selected CD34+ Cells and Defined Inoculum of T Cells From Related Haploidentical Donors for Older Patients With Indolent Hematologic Malignancies
Study Start Date :
Aug 1, 2000
Actual Primary Completion Date :
Dec 1, 2010
Actual Study Completion Date :
Dec 1, 2010

Arms and Interventions

ArmIntervention/Treatment
Experimental: Transplantation of CD34+ cells

Week #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started.

Procedure: non-myeloablative hematopoietic cell transplantation
TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil.
Other Names:
  • Peripheral-blood stem-cell transplantation
  • Drug: Anti-Thymocyte Globulin
    1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes.
    Other Names:
  • ATG
  • Drug: Cyclosporine
    6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin).
    Other Names:
  • INN/BAN
  • USAN
  • CSA
  • Drug: Mycophenolate Mofetil
    15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively which blocks the de nobo synthesis of guanosine required for DNA synthesis and has an effect on T and B cells.
    Other Names:
  • MMF
  • CellCept
  • Drug: G-CSF
    16 mg/kg, SQ Growth factor used to make bone marrow produce more blood cells
    Other Names:
  • Granulocyte colony-stimulating factor
  • CSF 3
  • Drug: Solumedrol
    1.0 mg/kg IV 2 hours prior to ATG Used to treat severe inflamation
    Other Names:
  • 6-Methylprednisolone
  • Methylprednisolone Acetate
  • Methylprednisolone Sodium Succinate
  • Drug: Acetaminophen
    650 mg PO, 30 minutes prior to infusion Pain reliever
    Other Names:
  • Tylenol
  • Drug: Diphenydramine
    50 mg IV, 30 minutes prior to infusion Used to relieve allergy symptoms
    Other Names:
  • Benadryl
  • Allermax
  • Q-Dryl
  • Diphen Cough
  • Drug: Hydrocortisone
    100 mg IV, 1 hour prior to infusion Used to relieve itching, redness and swelling of the skin
    Other Names:
  • Hydrocortisone Sodium Phosphate
  • Outcome Measures

    Primary Outcome Measures

    1. Engraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning [100 days]

      number achieving donor cell engraftment (>95%) by day 90 after transplant.

    Secondary Outcome Measures

    1. Acute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant [90 days]

      GVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Months and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age ≥ 50 years with hematologic malignancies treatable by a mixed chimera allogeneic HCT.

    • For patients ≤ 50 years of age with hematologic malignacies treatable with mixed chimera HCT who because of pre-exisiting medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional transplants.

    • Indolent advanced stage NHL, CLL, HD - Must have received and failed front-line therapy.

    • Multiple myeloma (Stage II or III) - Must have received prior chemotherapy. Consolidation after prior autografting is permitted.

    • AML/ALL - Must be in complete hematologic remission and have received cytotoxic chemotherapy at some stage before transplant. Patients with molecular or cytogenetic relapse will be accepted providing a donor is available. Patients with persistent or refractory disease will be considered on a case by case basis and transplants must be approved by the principal investigator.

    • CML - Patients will be accepted in chronic or accelerated phase. Patients who have received prior autografts after high dose therapy or have undergone intensive chemotherapy for either peripheral blood stem cell mobilization or treatment of advanced CML may be enrolled provided they are in CR, chronic phase or accelerated phase.

    • MDS - All patients with MDS will be eligible for this protocol, however, those patients with >10% blasts will require chemotherapy to reduce the blast % to < 10%.

    • SAA - Patients with severe aplastic anemia who have failed front line therapy.

    • A fully HLA-identical sibling donor is not available.

    • A matched unrelated donor has not been identified.

    • A haploidentical related donor is available who is in good health and does not have contraindications to donation.

    Exclusion Criteria:
    • Patients with rapidly progressive intermediate or high grade NHL

    • Uncontrolled CNS involvement with disease

    • Fertile men

    • Women unwilling to use contraceptive techniques during and for 12 months following treatment

    • Females who are pregnant

    • Cardiac function: ejection fraction < 30% or cardiac failure requiring therapy

    • Pulmonary: DLCO < 40% predicted and/or receiving supplementary continuous oxygen

    • Liver function abnormalities: elevation of bilirubin to > 4 mg/dl and/or transaminases

    3x the upper limit of normal. If hyperbilirubinemai is due to a known cause that will not increase the risks of transplant, than this upper limit may be exceeded.

    • Renal: creatinine clearance < 50 cc/min (24 hour urine collection)

    • Karnofsky performance score < 60%

    • Patients with poorly controlled hypertension.

    • Documented fungal disease that persists despite treatment

    • HIV positive patients.

    • Hepatitis B and C positive patients will be evaluated on a case by case basis

    • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or principal investigator would place the patient at unacceptable risk from this regimen.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Stanford University School of MedicineStanfordCaliforniaUnited States94305

    Sponsors and Collaborators

    • Stanford University

    Investigators

    • Principal Investigator: Robert Lowsky, Stanford University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Robert Lowsky, Associate Professor of Medicine, Stanford University
    ClinicalTrials.gov Identifier:
    NCT00185692
    Other Study ID Numbers:
    • IRB-13371
    • 75117
    • BMT124
    First Posted:
    Sep 16, 2005
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Jan 1, 2015

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleTransplating of CD34+ Selected Hematopietic Cells
    Arm/Group Description
    Period Title: Overall Study
    STARTED16
    COMPLETED0
    NOT COMPLETED16

    Baseline Characteristics

    Arm/Group TitleTransplating of CD34+ Selected Hematopietic Cells
    Arm/Group Description
    Overall Participants16
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    52
    Sex: Female, Male (Count of Participants)
    Female
    6
    37.5%
    Male
    10
    62.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    25%
    Not Hispanic or Latino
    12
    75%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    6.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    14
    87.5%
    More than one race
    1
    6.3%
    Unknown or Not Reported
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitleEngraftment of Haploidentical CD34+ Selected Blood Stem Cells in Older Patients or Those With Medical Co-morbidities Following Total Lymphoid Irradiation and Antithymocyte Globulin Transplant Conditioning
    Descriptionnumber achieving donor cell engraftment (>95%) by day 90 after transplant.
    Time Frame100 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTransplantation of CD34+ Cells
    Arm/Group DescriptionWeek #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started. non-myeloablative hematopoietic cell transplantation: TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil. Anti-Thymocyte Globulin: 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes. Cyclosporine: 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin). Mycophenolate Mofetil: 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively
    Measure Participants16
    Count of Participants [Participants]
    4
    25%
    2. Secondary Outcome
    TitleAcute Graft-versus-Host Disease (GVHD) Grade 2-4 Risk From Time of Transplant Until Day 90 Post-transplant
    DescriptionGVHD grading system goes from 0-4 where grade 4 is the most severe. Grade 0 and 1 do not require systemic treatment, Grade 2-4 require treatment. This trial evaluated the risk of developing acute GVHD grades 2-4 within 90 days of transplant.
    Time Frame90 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTransplantation of CD34+ Cells
    Arm/Group DescriptionWeek #1: Total Lymphoid Inrradiation (TLI) 120 cGy + Anti-thymocyte Globulin (ATG) 1.5 mg/kg + Solumedrol 1.0 mg/kg Daily for 5 days. Week #2: TLI 120 cGy (3 days a week, double on the 4th day) 5 days of CSP (oraly) one day after TLI was started. 3 days of MMF 4 days after TLI was started. non-myeloablative hematopoietic cell transplantation: TLI and ATG infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil. Anti-Thymocyte Globulin: 1.5 mg/kg QD x 5, IV. Dosage will be based on body weight. Purified, sterile IgG fraction of immune serum of rabbits immumixied with human thymus lymphocyte. This drug acts to modify the number and function of lymphocytes. Cyclosporine: 6.25 mg/kg BID, PO.Mechanism of action is inhibition of T-cell activation by binding to a cytoplasmic protein (cyclophillin). Mycophenolate Mofetil: 15 mg/kg Q 8 hours, PO. Inhibtis the enzme inosine monophsophate dehydrogenase (MPDII) noncompetitively
    Measure Participants16
    Count of Participants [Participants]
    1
    6.3%

    Adverse Events

    Time Frame120 days
    Adverse Event Reporting Description Non-serious adverse events were not collected.
    Arm/Group TitleCD34+ Selected Hematopietic Cells
    Arm/Group Description
    All Cause Mortality
    CD34+ Selected Hematopietic Cells
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    CD34+ Selected Hematopietic Cells
    Affected / at Risk (%)# Events
    Total14/16 (87.5%)
    General disorders
    Death14/16 (87.5%) 14
    Other (Not Including Serious) Adverse Events
    CD34+ Selected Hematopietic Cells
    Affected / at Risk (%)# Events
    Total0/0 (NaN)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleRobert Lowsky
    OrganizationStanford University
    Phone650-723-0822
    Emailrlowsky@stanford.edu
    Responsible Party:
    Robert Lowsky, Associate Professor of Medicine, Stanford University
    ClinicalTrials.gov Identifier:
    NCT00185692
    Other Study ID Numbers:
    • IRB-13371
    • 75117
    • BMT124
    First Posted:
    Sep 16, 2005
    Last Update Posted:
    Dec 4, 2019
    Last Verified:
    Jan 1, 2015