Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Autologous and Allogeneic Transplant for Relapsed Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00802113
Recruitment Status : Completed
First Posted : December 4, 2008
Results First Posted : March 27, 2019
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Prakash Satwani, Columbia University

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
Non-Hodgkin's Lymphoma Hodgkins Disease Drug: Fludarabine Drug: Busulfan Drug: Anti-Thymocyte Globulin 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : June 2003
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 22, 2014


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 Name: Fludara

Drug: Busulfan
Busulfan 3.2 mg/kg/day x 2 days
Other Name: 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 Name: Fludara

Drug: Busulfan
Busulfan 3.2 mg/kg/day x 2 days
Other Name: Busulfex

Drug: Anti-Thymocyte Globulin
Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days
Other Name: ATG




Primary Outcome Measures :
  1. Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 1 year post-transplantation ]
    Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.

  2. Time to Platelet Engraftment [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 1 year post-transplantation ]
    Status as subjects died post-AlloHCT



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00802113


Locations
Layout table for location information
United States, Illinois
Children's Memorial Hospital in Chicago
Chicago, Illinois, United States, 60611
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27708
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Columbia University
Investigators
Layout table for investigator information
Principal Investigator: Prakash Satwani, MD Columbia University

Layout table for additonal information
Responsible Party: Prakash Satwani, Assistant Professor of Clinical Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT00802113    
Other Study ID Numbers: AAAA5185
CHNY-01-501 ( Other Identifier: CUMC )
First Posted: December 4, 2008    Key Record Dates
Results First Posted: March 27, 2019
Last Update Posted: March 27, 2019
Last Verified: March 2019
Keywords provided by Prakash Satwani, Columbia University:
Autologous Stem Cell Transplant
Cord Blood Transplant
Allogeneic Stem Cell Transplant
Relapsed Lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Busulfan
Antilymphocyte Serum
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists