Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00038857
Collaborator
(none)
29
1
1
93
0.3

Study Details

Study Description

Brief Summary

Donor:

This clinical study will evaluate the feasibility of a purified CD34 peripheral blood progenitor cell (PBPC) transplants in patients with hematological malignancies.

The primary objectives of the study are to evaluate the recipient obtaining donor derived neutrophil engraftment and the incidence of acute graft versus host disease [GvHD] (grade III-IV).

Secondary objectives include assessments of recipient having donor derived platelet engraftment, incidence of graft failure and chronic GvHD, overall and disease free survival, clinical safety and device performance of the CliniMACS CD34 selection device.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Donor Description:

Before taking part in this study, donors will have an evaluation that is the standard for any bone marrow or blood stem cell donor. These include standard blood tests, an electrocardiogram (EKG), and a chest X-ray. Donors will also be given a general health questionnaire that is given to all blood donors in the United States. It should take no more than 10 minutes to complete the questionnaire.

Donors in this study will receive standard mobilization therapy with daily G-CSF every 12 hours. The Granulocyte colony-stimulating factor (G-CSF) will be given as an injection under the skin. The mobilization phase starts on the first day that donors receive G-CSF and continues until the final day of the stem cell collection process (leukapheresis).

Donors in this study will receive Neupogen (white blood cell growth factor) to stimulate the immature blood cells. They will receive two injections, twice a day for four days. On the fourth day, assuming they have enough immature white blood cells, researchers will start the stem cell collection process (leukapheresis).

The stem cell collection will go from 1 to 4 days until enough immature cells have been collected, but will not be done on any day the donor's platelet count falls below 75,000. The stem cell is called a CD34(+) cell. These cells will then be processed over a cell-processing machine to try to purify the immature fraction of cells and remove the T-lymphocytes that are part of the fatal graft versus host disease. The T-cell is called a CD3(+) cell.

Leukapheresis, with later CD34(+) cell selection, will start on the day when circulating CD34(+) count is at a high enough level. Leukapheresis will continue until the appropriate count is reached. If the CD3(+) count is too high, adjustments will be made.

For those donors who cannot reach the collection goal in one series of collection attempts, researchers will wait until the donor recovers from the first stem cell collection and try again. If the donor is unable to reach the collection goal again, another attempt will be made with a different donor.

The blood thinner used for the procedure will be acid citrate dextrose (ACD). Heparin may be substituted when clinically needed. No additional blood thinners or additives should be added beyond those normally used during leukapheresis. A unique identification and labeling system shall be used to track the leukapheresis product from collection to infusion.

Samples will be taken from each leukapheresis product pre- and post-selection for quality analysis.

This is an investigational study. No more than 90 donors will take part in this study. All will be enrolled at M. D. Anderson.

Recipient Description:

Before taking part in this study, recipients will have standard evaluations to determine the stage of their disease. These may include bone marrow aspirations and biopsies and if necessary, CT scans and chest x-rays. All recipients will go through cardiopulmonary evaluation.

The recipients will have an allogeneic bone marrow transplant with pre-treatment of thiotepa, fludarabine, melphalan, and antithymocyte globulin. This will be followed by infusion of the peripheral blood progenitor cells.

Recipients will have daily follow-up exams in the hospital. Recipients will be evaluated at least one to five times per week after they leave until Day 100. After that, they will have evaluations at least once every three months until about one year and then once every six months.

The CliniMACS device is being provided by used of an investigational device exemption for the FDA. Without the CliniMACS device, this procedure would not be possible.

This is an investigational study. A total of 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Megadose CD34 Selected Progenitor Cells for Transplantation in Patients With Advanced Hematological Malignant Diseases
Study Start Date :
Sep 1, 2001
Actual Primary Completion Date :
Jun 1, 2009
Actual Study Completion Date :
Jun 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: CD34 PBPC

CD34 peripheral blood progenitor cell (PBPC) transplants in 3 groups: 1) HLA-matched Sibling Transplant Patients; 2) Unrelated Donor Transplant Patients; 3) Haplo Identical Transplant Patients. Preparative regimen is 140 mg/m^2 Melphalan on day -8, 10 mg/kg Thiotepa on day -7, 160 mg/m^2 Fludarabine over 4 days on days -6, -5, -4, -3 and 1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.

Procedure: Megadose of CD34 Selected Progenitor Cells
Haploidentical peripheral blood progenitor cell (PBPC) transplants on Day 0.

Drug: Melphalan
140 mg/m^2 on day -8
Other Names:
  • Alkeran
  • Drug: Thiotepa
    10 mg/kg on day -7

    Drug: Fludarabine
    160 mg/m^2 over 4 days on days -6, -5, -4, -3
    Other Names:
  • Fludarabine Phosphate
  • Fludara
  • Drug: Rabbit ATG
    1.5 mg/kg of Rabbit ATG a day times 4 over 4 days on days -6, -5, -4, -3.
    Other Names:
  • Rabbit antithymocyte globulin
  • ATG
  • rATG
  • Genzyme
  • Thymoglobulin
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Absolute Neutrophil Count Engraftment [Day 0 up to Day 30]

      Absolute neutrophil engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 * 10^9/L. Baseline to Day 30 post transplant.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male or female recipients must have histopathologically confirmed diagnosis of hematological or lymphatic malignancy in one of the following categories:

    2. Acute Leukemia: Recipients must have acute leukemia in second or greater remission in relapse, or primary refractory disease. Acute leukemia (in first remission with poor risk factors and molecular prognosis; acute myelogenous leukemia (AML) with -5, -7, t(6:9), +8, -11q23 and Acute lymphoblastic leukemia (ALL) with Phil+ t(9:22), t(4:11) and secondary remission inclusive).

    3. Chronic myelogenous leukemia: Chronic Myeloid Leukemia (CML) in accelerated phase, blast crisis or second chronic phase.

    4. Myelodysplastic syndrome (in high and intermediate risk categories) - marrow blast > 10% on differential.

    5. Non-Hodgkin's lymphoma in relapse

    6. Refractory chronic lymphoid leukemia (CLL) - refractory to fludarabine based regimen, unrelated donor and haploidentical only

    7. The recipient must be <=60 years old at time of registration.

    8. The recipient must have a related donor haploidentical for human leukocyte antigen (HLA), A, B, C, or DR loci. They may be partial matched on the other haplotype.

    9. Recovery from prior therapy, chemotherapy, or radiotherapy, as defined by: Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 2; have recovered from the toxicity of prior major chemotherapy at the start of the preparative regimen on this protocol

    10. Adequate cardiac and pulmonary function (Left ventricular ejection fraction (LVEF)

    45%, Carbon Monoxide Diffusing Capacity (DL CO)>50% corrected for hemoglobin)

    1. Serum creatinine <1.5 mg/dL or creatinine clearance >50 ml/min for those above serum creatinine of 1.5; serum bilirubin <2.0 mg/dL; Aspartate transaminase (AST)/alanine aminotransferase (ALT) <2* Upper limits of normal (ULN) (unless secondary to disease)

    2. Females of childbearing potential must have a negative serum or urine beta-HCG test within three weeks of registration. Patients will be informed of the risk of not receiving adequate contraception.

    3. No prior cancer within five years with the exception of surgically cured non-melanoma skin cancer or in situ cancer of the cervix

    4. The recipient and/or the recipient's legal guardian must have been informed of the investigational nature of this study and have signed a consent form which is in accordance with Federal guidelines and the guidelines of the participating institution.

    5. Donor age must be 4-80 years and weight greater than 20 kg.

    6. Medical history and physical examination confirm good health status as defined by institutional standards

    7. Seronegative for HIV Ag, HIV 1+2 Ab, Human T Cell Leukemia Virus (HTLV) I/II Ab, HbsAg, HbcAb (IgM [combination screening test] and IgG), HCV, RPR for syphilis within 30 days of apheresis collection - If positive for Hepatitis B or C or syphilis, the recipient must be notified - the recipient may proceed if PI, recipient and donor agree and there is no substitute donor

    8. HLA matching criteria

    9. Female donors of child-bearing potential must have a negative serum or urine beta-HCG test within three weeks of mobilization

    10. Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate

    11. Agreeable to second donation of PBPC (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant

    12. The donor, or legal guardian greater than 18 years of age, must have been informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines and the guidelines of the participating institution. If the donor is less than 18 years of age, parent or legal guardian consent must be obtained.

    13. The prospective donor will be screened for cytomegalovirus (CMV) seroreactivity and a seronegative donor will be utilized if available when the patient is seronegative.

    Exclusion Criteria:
    1. Participation in other clinical trials which involve investigational drugs or devices that might influence the endpoints of this study

    2. Evidence of active hepatitis (B and/or C) or cirrhosis

    3. Neither the recipient nor the donor may be HIV positive

    4. Presence of any other active, uncontrolled bacterial, viral or fungal infection.

    5. Uncontrolled central nervous system (CNS) involvement with tumor cells

    6. Documented allergy to murine proteins or iron dextran

    7. The recipient is a lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.

    8. Severe end-organ dysfunctions, particularly neurologic deficits detectable by clinical examination or significant intellectual impairment in metabolic disorders

    9. Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or hepatitis (on screening).

    10. Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.

    11. Factors that place the donor at increased risk for complications from leukapheresis or G-CSF therapy such as pulmonary hypertension, coronary artery disease, peripheral vascular disease, cerebral vascular disease.

    12. Lactating female or, if of child-bearing potential, is unwilling to implement adequate birth control.

    13. Donors who are hepatitis positive, Human T-cell lymphotropic virus type I (HTLVI) positive need consent of Principal Investigator and determination that this is the best donor.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center

    Investigators

    • Principal Investigator: Richard E. Champlin, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00038857
    Other Study ID Numbers:
    • ID01-220
    First Posted:
    Jun 7, 2002
    Last Update Posted:
    Aug 10, 2012
    Last Verified:
    Aug 1, 2012

    Study Results

    Participant Flow

    Recruitment Details Recruitment Period:October 1, 2001 to November 1, 2008. All participants recruited at UT MD Anderson Cancer Center.
    Pre-assignment Detail Of the 29 participants enrolled, one participant was excluded from the trial and did not receive any treatment.
    Arm/Group Title CD34 PBPC
    Arm/Group Description Melphalan 140 mg/m^2 given IV for one day. Thiotepa 10 mg/kg given IV for one day. Fludarabine 40 mg/m^2 given IV daily for four days. Rabbit ATG 1.5 mg/kg given IV daily for four days. Stem Cell Infusion of CD34+ Selected Cells given on Day 0.
    Period Title: Overall Study
    STARTED 29
    COMPLETED 28
    NOT COMPLETED 1

    Baseline Characteristics

    Arm/Group Title CD34 PBPC
    Arm/Group Description Melphalan 140 mg/m^2 given IV for one day. Thiotepa 10 mg/kg given IV for one day. Fludarabine 40 mg/m^2 given IV daily for four days. Rabbit ATG 1.5 mg/kg given IV daily for four days. Stem Cell Infusion of CD34+ Selected Cells given on Day 0.
    Overall Participants 29
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    36
    (11)
    Sex: Female, Male (Count of Participants)
    Female
    13
    44.8%
    Male
    16
    55.2%
    Region of Enrollment (participants) [Number]
    United States
    29
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Absolute Neutrophil Count Engraftment
    Description Absolute neutrophil engraftment defined as first of 3 consecutive days with Absolute neutrophil count (ANC) equal to or more than 0.5 * 10^9/L. Baseline to Day 30 post transplant.
    Time Frame Day 0 up to Day 30

    Outcome Measure Data

    Analysis Population Description
    Analysis per protocol.
    Arm/Group Title Melphalan + Thiotepa + Fludarabine + Rabbit ATG + CD34 PBPC
    Arm/Group Description Melphalan 140 mg/m^2 given for one day. Thiotepa 10 mg/kg given for one day. Fludarabine 40 mg/m^2 given daily for four days. Rabbit ATG 1.5 mg/kg given daily for four days. Infusion of CD34+ Selected Cells given on Day 0.
    Measure Participants 28
    Number [participant]
    21

    Adverse Events

    Time Frame 7 Years, 1 Month (October 1, 2001 to November 1, 2008)
    Adverse Event Reporting Description
    Arm/Group Title CD34 PBPC
    Arm/Group Description Melphalan 140 mg/m^2 given IV for one day. Thiotepa 10 mg/kg given IV for one day. Fludarabine 40 mg/m^2 given IV daily for four days. Rabbit ATG 1.5 mg/kg given IV daily for four days. Stem Cell Infusion of CD34+ Selected Cells given on Day 0.
    All Cause Mortality
    CD34 PBPC
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    CD34 PBPC
    Affected / at Risk (%) # Events
    Total 21/28 (75%)
    Blood and lymphatic system disorders
    Hemolysis 1/28 (3.6%) 1
    Thrombotic Microangiopathy 1/28 (3.6%) 1
    Cardiac disorders
    Cardiac Failure 1/28 (3.6%) 1
    Gastrointestinal disorders
    Mucositis 2/28 (7.1%) 2
    General disorders
    Graft Failure 6/28 (21.4%) 6
    Fever 9/28 (32.1%) 9
    Disease Relapse 4/28 (14.3%) 4
    Graft vs Host Disease 2/28 (7.1%) 2
    Death 4/28 (14.3%) 4
    Hepatobiliary disorders
    Elevated alanine aminotransferase (ALT) 1/28 (3.6%) 1
    Infections and infestations
    Infection 17/28 (60.7%) 17
    Metabolism and nutrition disorders
    Hypokalemia 1/28 (3.6%) 1
    Nervous system disorders
    Neuropathy 1/28 (3.6%) 1
    Encephalopathy 1/28 (3.6%) 1
    Renal and urinary disorders
    Left Ureteral Obstruction 1/28 (3.6%) 1
    Renal Failure 2/28 (7.1%) 2
    Respiratory, thoracic and mediastinal disorders
    Respiratory Failure 5/28 (17.9%) 5
    Diffuse Alveolar Hemorrhage 3/28 (10.7%) 3
    Other (Not Including Serious) Adverse Events
    CD34 PBPC
    Affected / at Risk (%) # Events
    Total 28/28 (100%)
    Blood and lymphatic system disorders
    Low Platelets 1/28 (3.6%) 1
    Cardiac disorders
    Hypertension 1/28 (3.6%) 1
    Eye disorders
    Diplopia 1/28 (3.6%) 1
    Gastrointestinal disorders
    Diarrhea 10/28 (35.7%) 10
    Mucositis 11/28 (39.3%) 11
    Gastrointestinal Bleed 1/28 (3.6%) 1
    Nausea 14/28 (50%) 14
    General disorders
    Fever 4/28 (14.3%) 4
    Neutropenic Fever 7/28 (25%) 7
    Fluid Overload 1/28 (3.6%) 1
    Graft versus Host Disease 7/28 (25%) 7
    Hepatobiliary disorders
    Elevated Alkaline Phosphatase 1/28 (3.6%) 1
    Elevated Alanine Aminotransferase 1/28 (3.6%) 1
    Elevated Bilirubin 2/28 (7.1%) 2
    Infections and infestations
    BK Virus 3/28 (10.7%) 3
    Infecrtion 14/28 (50%) 14
    Renal and urinary disorders
    Elevated Creatinine 2/28 (7.1%) 2
    Hemorrhagic Cystitis 6/28 (21.4%) 6
    Respiratory, thoracic and mediastinal disorders
    Cough 1/28 (3.6%) 1
    Bronchiolitis 1/28 (3.6%) 1
    Pneumonia 3/28 (10.7%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT 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/Title Dr. Richard E. Champlin
    Organization MDAnderson Cancer Center
    Phone 713-792-8750
    Email celsaenz@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00038857
    Other Study ID Numbers:
    • ID01-220
    First Posted:
    Jun 7, 2002
    Last Update Posted:
    Aug 10, 2012
    Last Verified:
    Aug 1, 2012