Autologous and Allogeneic Transplant for Relapsed Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
Prakash Satwani, Columbia University
ClinicalTrials.gov Identifier:
NCT00802113
First received: May 5, 2008
Last updated: April 22, 2015
Last verified: April 2015
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Columbia University:

Primary Outcome Measures:
  • Determination of response rates [ Time Frame: Up to 1 year post-transplantation ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

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
Study First Received: May 5, 2008
Last Updated: April 22, 2015
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on August 02, 2015