Autologous and Allogeneic Transplant for Relapsed Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00802113
• Other study ID #: AAAA5185
• Secondary ID: CHNY-01-501
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2003
• Est. completion date: October 22, 2014

Study information

• Verified date: March 2019
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 22, 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkins Disease
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Drug:
• Fludarabine
Fludarabine 30 mg/m2 x 5 days
• Busulfan
Busulfan 3.2 mg/kg/day x 2 days
• Anti-Thymocyte Globulin
Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days

Locations

Country	Name	City	State
United States	Children's Memorial Hospital in Chicago	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 1 year post-transplantation
Primary	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.	Up to 1 year post-transplantation
Primary	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.	Up to 1 year post-transplantation
Secondary	Time to Neutrophil Engraftment	Following MAC AutoSCT, the median time to neutrophil (PMN) recovery will be measured.	Up to 1 year post-transplantation
Secondary	Time to Platelet Engraftment	Following MAC AutoSCT, the median time to platelet recovery will be measured.	Up to 1 year post-transplantation
Secondary	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.	Up to 1 year post-transplantation
Secondary	Total Number of Subjects That Experienced Transplant-related Mortality (TRM)	Status as subjects died post-AlloHCT	Up to 1 year post-transplantation