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Autologous and Allogeneic Transplant for Relapsed Lymphoma

Primary Purpose

Non-Hodgkin's Lymphoma, Hodgkins Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Busulfan
Anti-Thymocyte Globulin
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring Autologous Stem Cell Transplant, Cord Blood Transplant, Allogeneic Stem Cell Transplant, Relapsed Lymphoma

Eligibility Criteria

undefined - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

      1. Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy)
      2. 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).
      3. Second relapse.
      4. 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

Sites / Locations

  • Children's Memorial Hospital in Chicago
  • Hackensack University Medical Center
  • Columbia University Medical Center
  • New York Medical College
  • Duke University
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A - Family Donor

Arm B - Unrelated Cord Blood or Adult

Arm 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. 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.

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.

Outcomes

Primary Outcome Measures

Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)
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.
Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT
Includes subjects with any measurable growth of disease in a previously affected site or detection of disease in a new site confirmed by biopsy.
Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT
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

Time to Neutrophil Engraftment
Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.
Time to Platelet Engraftment
Following MAC AutoSCT, the median time to platelet recovery will be measured.
Total Number of Subjects With Grade II-IV Acute Graft-versus-Host-Disease (GVHD)
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.
Total Number of Subjects That Experienced Transplant-related Mortality (TRM)
Status as subjects died post-AlloHCT

Full Information

First Posted
May 5, 2008
Last Updated
March 4, 2019
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT00802113
Brief Title
Autologous and Allogeneic Transplant for Relapsed Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 22, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Hodgkins Disease
Keywords
Autologous Stem Cell Transplant, Cord Blood Transplant, Allogeneic Stem Cell Transplant, Relapsed Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A - Family Donor
Arm Type
Experimental
Arm 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. 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.
Arm Title
Arm B - Unrelated Cord Blood or Adult
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine 30 mg/m2 x 5 days
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
Busulfan 3.2 mg/kg/day x 2 days
Intervention Type
Drug
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
ATG
Intervention Description
Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days
Primary Outcome Measure Information:
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
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
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
Secondary Outcome Measure Information:
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
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
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
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must have adequate organ function as below Adequate renal function defined as: Serum creatinine less than or equal to 2.0 x normal, or 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: Total bilirubin <2.0 x normal; or 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: Shortening fraction of >27% by echocardiogram, or Ejection fraction of >47% by radionuclide angiogram or echocardiogram Adequate pulmonary function defined as: Diffusing capacity of the lungs for carbon monoxide (DLCO) >50% by pulmonary function test for autologous transplant DLCO > 40% by pulmonary function test for reduced intensity allogeneic transplant 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: 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. Patients with 1st PR, 2nd CR, 2nd PR, or 2nd SD following reinduction chemotherapy Patients with 3rd CR, 3rd PR, 3rd SD following reinduction chemotherapy Patients with Hodgkin's Disease with either of the following: Primary induction failure (failure to achieve initial CR) and/or primary refractory disease. First relapse Early relapse (within 12 months off therapy) (excluding those who received no therapy or radiation therapy only for initial therapy) 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). Second relapse. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prakash Satwani, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Memorial Hospital in Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

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Autologous and Allogeneic Transplant for Relapsed Lymphoma

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