Autologous and Allogeneic Transplant for Relapsed Lymphoma

Sponsor
Columbia University (Other)
Overall Status
Completed
CT.gov ID
NCT00802113
Collaborator
(none)
30
6
2
136.7
5
0

Study Details

Study Description

Brief Summary

The sequential combination of myeloablative therapy and autologous stem cell transplantation (APBSCT) followed by a reduced intensity allogeneic stem cell transplant (Allo SCT) and post SCT adoptive cellular immunotherapy will be well tolerated in patients with refractory or recurrent non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Lymphomas are the third most common group of cancers in children and adolescents in the United States. While Hodgkin's Disease (HD) has been described for many years, some subtypes of the non-Hodgkin's Lymphomas (NHL) have only recently been described. Non-Hodgkin's lymphomas traditionally have been classified as low, intermediate or high grade based on their clinical aggressiveness. More recently they have been divided into two major subgroups indolent and aggressive lymphomas by the current National Cancer Institute (NCI/PDQ) reference. Among children, aggressive histologies are prevalent including small non-cleaved cell lymphoma, lymphoblastic lymphoma, and diffuse large cell lymphoma. The most common histologic classifications of childhood non-Hodgkin's lymphoma over the past 30 years has included the morphological schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic sub-groupings of the National Cancer Institute's Working Formulation, and the most recently developed classification that utilizes morphological, immunophenotypic and genetic information in the Revised European-American Lymphoma (REAL) classification.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Sequential Myeloablative Stem Cell Transplantation and Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma and Hodgkin's Disease
Study Start Date :
Jun 1, 2003
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Oct 22, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A - Family Donor

Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. The non-ablative therapy will be busulfan and fludarabine, Usually large (myeloablative) doses of these drugs are used for an allogeneic transplant. However, in this study lower doses (non-ablative) of chemotherapy will be given. In patients who still have evidence of disease after allogeneic transplant, additional donor immune cells (donor lymphocyte infusion) (DLI) will be given twice to further treat the lymphoma.

Drug: Fludarabine
Fludarabine 30 mg/m2 x 5 days
Other Names:
  • Fludara
  • Drug: Busulfan
    Busulfan 3.2 mg/kg/day x 2 days
    Other Names:
  • Busulfex
  • Experimental: Arm B - Unrelated Cord Blood or Adult

    Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. If a closely matched cord blood donor or unrelated adult donor is found, non-ablative chemotherapy with busulfan, fludarabine and antithymocyte globulin (ATG) followed by the infusion of matched unrelated cord blood cells or adult donor stem cells or bone marrow to restore the bone marrow will be given.

    Drug: Fludarabine
    Fludarabine 30 mg/m2 x 5 days
    Other Names:
  • Fludara
  • Drug: Busulfan
    Busulfan 3.2 mg/kg/day x 2 days
    Other Names:
  • Busulfex
  • Drug: Anti-Thymocyte Globulin
    Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days
    Other Names:
  • ATG
  • Outcome Measures

    Primary Outcome Measures

    1. Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT) [Up to 1 year post-transplantation]

      Complete Response is defined as the complete resolution of B symptoms (i.e., weight loss, night sweats and fever) and normalization of all sites of disease on the basis of physical exam, bone marrow biopsy, and imaging studies.

    2. Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT [Up to 1 year post-transplantation]

      Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.

    3. Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT [Up to 1 year post-transplantation]

      Total includes subjects with partial response and patients with stable disease, defined as <50% reduction in measurable disease or the uninterrupted persistence of B symptoms.

    Secondary Outcome Measures

    1. Time to Neutrophil Engraftment [Up to 1 year post-transplantation]

      Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.

    2. Time to Platelet Engraftment [Up to 1 year post-transplantation]

      Following MAC AutoSCT, the median time to platelet recovery will be measured.

    3. Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD) [Up to 1 year post-transplantation]

      The criteria for grading is based on extent of organ involvement (i.e., Skin, Liver and Gut - rash on >50% of skin, bilirubin 2-3 mg/dl, diarrhea > 500 ml/day) with Grade II being better outcome and Grade IV being worse outcome.

    4. Total Number of Subjects That Experienced Transplant-related Mortality (TRM) [Up to 1 year post-transplantation]

      Status as subjects died post-AlloHCT

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Patient must have adequate organ function as below

    • Adequate renal function defined as:
    1. Serum creatinine less than or equal to 2.0 x normal, or

    2. Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range

    • Adequate liver function defined as:
    1. Total bilirubin <2.0 x normal; or

    2. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SPGT) (alanine aminotransferase (ALT)) <5.0 x normal

    • Adequate cardiac function defined as:
    1. Shortening fraction of >27% by echocardiogram, or

    2. Ejection fraction of >47% by radionuclide angiogram or echocardiogram

    • Adequate pulmonary function defined as:
    1. Diffusing capacity of the lungs for carbon monoxide (DLCO) >50% by pulmonary function test for autologous transplant

    2. DLCO > 40% by pulmonary function test for reduced intensity allogeneic transplant

    3. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% in room air.

    Disease Status (Eligibility)

    • Patients with Non-Hodgkin's Lymphoma with either of the following:
    1. Primary induction failure (failure to achieve initial CR) who have a partial response (PR) or stable disease (SD) with reinduction chemotherapy. *All patients are required to have a biopsy regardless of positron emission tomography (PET)/Gallium results.

    2. Patients with 1st PR, 2nd CR, 2nd PR, or 2nd SD following reinduction chemotherapy

    3. Patients with 3rd CR, 3rd PR, 3rd SD following reinduction chemotherapy

    • Patients with Hodgkin's Disease with either of the following:
    1. Primary induction failure (failure to achieve initial CR) and/or primary refractory disease.

    2. First relapse

    3. Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy)

    4. Late relapse (greater than 12 months off therapy). Only patients with recurrent Stage III or IV disease and/or those with B symptoms at relapse (all other late relapses are excluded).

    5. Second relapse.

    6. Third relapse.

    • Patients must achieve a CR, PR or SD after reinduction chemotherapy.
    Exclusion Criteria:
    • Patients with NHL or HD with 4th or greater CR, PR, and/or SD

    • Patients with progressive disease (PD) unresponsive to reinduction chemo, radio, or immunotherapy

    • Hodgkin's Disease in late relapse (other than those discussed above).

    • Patients with post-transplant lymphoproliferative disease following a solid organ transplantation or AIDS associated NHL

    • Patients who don't have an eligible donor

    • Women who are pregnant

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Memorial Hospital in Chicago Chicago Illinois United States 60611
    2 Hackensack University Medical Center Hackensack New Jersey United States 07601
    3 Columbia University Medical Center New York New York United States 10032
    4 New York Medical College Valhalla New York United States 10595
    5 Duke University Durham North Carolina United States 27708
    6 Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Columbia University

    Investigators

    • Principal Investigator: Prakash Satwani, MD, Columbia University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Prakash Satwani, Assistant Professor of Clinical Pediatrics, Columbia University
    ClinicalTrials.gov Identifier:
    NCT00802113
    Other Study ID Numbers:
    • AAAA5185
    • CHNY-01-501
    First Posted:
    Dec 4, 2008
    Last Update Posted:
    Mar 27, 2019
    Last Verified:
    Mar 1, 2019
    Keywords provided by Prakash Satwani, Assistant Professor of Clinical Pediatrics, Columbia University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Out of the 30 enrolled subjects, only 23 subjects received both MAC and AutoSCT and Reduced Intensity Conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT). 7 subjects did not complete the transplantation and therefore were not included into data analysis.
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Period Title: Overall Study
    STARTED 6 17
    COMPLETED 6 17
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult Total
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world. Total of all reporting groups
    Overall Participants 6 17 23
    Age (Count of Participants)
    <=18 years
    4
    66.7%
    13
    76.5%
    17
    73.9%
    Between 18 and 65 years
    2
    33.3%
    4
    23.5%
    6
    26.1%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    7
    41.2%
    8
    34.8%
    Male
    5
    83.3%
    10
    58.8%
    15
    65.2%

    Outcome Measures

    1. Primary Outcome
    Title Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)
    Description Complete Response is defined as the complete resolution of B symptoms (i.e., weight loss, night sweats and fever) and normalization of all sites of disease on the basis of physical exam, bone marrow biopsy, and imaging studies.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Count of Participants [Participants]
    4
    66.7%
    12
    70.6%
    2. Primary Outcome
    Title Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
    Description Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Count of Participants [Participants]
    1
    16.7%
    3
    17.6%
    3. Primary Outcome
    Title Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT
    Description Total includes subjects with partial response and patients with stable disease, defined as <50% reduction in measurable disease or the uninterrupted persistence of B symptoms.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Count of Participants [Participants]
    4
    66.7%
    9
    52.9%
    4. Secondary Outcome
    Title Time to Neutrophil Engraftment
    Description Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Mean (Full Range) [days]
    16
    24
    5. Secondary Outcome
    Title Time to Platelet Engraftment
    Description Following MAC AutoSCT, the median time to platelet recovery will be measured.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    1 subject under Arm A and 2 subject under Arm B did not have this data point collected and therefore 3 subjects were not included into analysis.
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 5 15
    Mean (Full Range) [days]
    22
    53
    6. Secondary Outcome
    Title Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD)
    Description The criteria for grading is based on extent of organ involvement (i.e., Skin, Liver and Gut - rash on >50% of skin, bilirubin 2-3 mg/dl, diarrhea > 500 ml/day) with Grade II being better outcome and Grade IV being worse outcome.
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    Subjects who completed RIC AlloHCT
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Number [participants]
    0
    0%
    7
    41.2%
    7. Secondary Outcome
    Title Total Number of Subjects That Experienced Transplant-related Mortality (TRM)
    Description Status as subjects died post-AlloHCT
    Time Frame Up to 1 year post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    Measure Participants 6 17
    Number [participants]
    2
    33.3%
    6
    35.3%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Arm/Group Description Fludarabine and Busulfan: Patients who have a matched family (allogeneic) donor will go on to receive non-ablative therapy, followed by an infusion of donor stem cells; this is called an allogeneic peripheral blood stem cell transplant. Fludarabine, Busulfan and ATG: For patients who don't have a matched family donor, a cord blood search and unrelated adult search will be done at all of the cord blood banks and adult donor registries in the world.
    All Cause Mortality
    Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/6 (33.3%) 6/17 (35.3%)
    Serious Adverse Events
    Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/17 (0%)
    Other (Not Including Serious) Adverse Events
    Arm A - Family Donor Arm B - Unrelated Cord Blood or Adult
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/17 (0%)

    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/Title Prakash Satwani, MD
    Organization Columbia University
    Phone (212) 305-0223
    Email ps2087@cumc.columbia.edu
    Responsible Party:
    Prakash Satwani, Assistant Professor of Clinical Pediatrics, Columbia University
    ClinicalTrials.gov Identifier:
    NCT00802113
    Other Study ID Numbers:
    • AAAA5185
    • CHNY-01-501
    First Posted:
    Dec 4, 2008
    Last Update Posted:
    Mar 27, 2019
    Last Verified:
    Mar 1, 2019