We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Autologous and Allogeneic Transplant for Relapsed Lymphoma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00802113
First Posted: December 4, 2008
Last Update Posted: October 12, 2017
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.
Collaborator:
Duke University
Information provided by (Responsible Party):
Prakash Satwani, Columbia University
  Purpose
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 Intervention Phase
Non-Hodgkin's Lymphoma Hodgkins Disease Drug: Fludarabine and Busulfan Drug: Fludarabine, Busulfan and ATG Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Prakash Satwani, Columbia University:

Primary Outcome Measures:
  • Determination of response rates [ Time Frame: Up to 1 year post-transplantation ]
    Those patients with measurable disease at the time of study entry will have determination of response.

  • Rate of progression-free distribution [ Time Frame: Up to 1 year post-transplantation ]
    The progression-free for each arm will be estimated using the product-limit method (Kaplan-Meier).

  • Incidence of toxicities [ Time Frame: Up to 1 year post-transplantation ]
    The incidence and severity of toxicities will be monitored according to National Cancer Institute (NCI) Common Toxicity Criteria Version 2

  • Overall survival distribution rate [ Time Frame: Up to 1 year post-transplantation ]
    The overall survival distribution for each arm will be estimated using the product-limit method (Kaplan-Meier).


Secondary Outcome Measures:
  • Distribution of time to neutrophil engraftment [ Time Frame: Up to 1 year post-transplantation ]
    The distribution of the time to neutrophil engraftment following non-myeloablative alloSCT, stratified by cell source, HLA disparity, and cell dose, will be estimated using the product-limit method (Kaplan-Meier).

  • Distribution of the time to platelet engraftment [ Time Frame: Up to 1 year post-transplantation ]
    The distribution of the time to platelet engraftment following non-myeloablative alloSCT, stratified by cell source, HLA disparity, and cell dose, will be estimated using the product-limit method (Kaplan-Meier).

  • Incidence of acute and chronic graft vs. host disease [ Time Frame: Up to 1 year post-transplantation ]
    The incidence and severity of acute and chronic graft vs. host disease, stratified by cell source and HLA disparity will be estimated.


Enrollment: 31
Study Start Date: June 2003
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
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 and Busulfan
Fludarabine 30 mg/m2 x 5 days Busulfan 3.2 mg/kg/day x 2 days GVHD Prophylaxis with MMF and FK506
Other Names:
  • Fludara
  • Busulfex
Experimental: Arm B
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 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, Busulfan and ATG
Fludarabine 30 mg/m2 x 5 days Busulfan 3.2 mg/kg/day x 2 days Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days GVHD Prophylaxis with MMF and FK506
Other Names:
  • Fludara
  • Busulfex
  • ATG

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.
  Eligibility

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.


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 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. SGOT (AST) or SGPT (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. DLCO >50% by pulmonary function test for autologous transplant
    2. DLCO > 40% by pulmonary fuction 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 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 intial 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
  Contacts and Locations
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
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Duke University
Investigators
Principal Investigator: Prakash Satwani, MD Columbia University
  More Information

Responsible Party: Prakash Satwani, Assistant Professor of Clinical Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT00802113     History of Changes
Other Study ID Numbers: AAAA5185
CHNY-01-501 ( Other Identifier: CUMC )
First Submitted: May 5, 2008
First Posted: December 4, 2008
Last Update Posted: October 12, 2017
Last Verified: April 2015

Keywords provided by Prakash Satwani, Columbia University:
Autologous Stem Cell Transplant
Cord Blood Transplant
Allogeneic Stem Cell Transplant
Relapsed Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Busulfan
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists