Autologous and Allogeneic Transplant for Relapsed Lymphoma

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00802113

Enrollment

Registered

2008-12-04

Start date

2003-06-30

Completion date

2014-10-22

Last updated

2019-03-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hodgkins Disease, Non-Hodgkin's Lymphoma

Keywords

Autologous Stem Cell Transplant, Cord Blood Transplant, Allogeneic Stem Cell Transplant, Relapsed Lymphoma

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.

Interventions

DRUGFludarabine

Fludarabine 30 mg/m2 x 5 days

DRUGBusulfan

Busulfan 3.2 mg/kg/day x 2 days

DRUGAnti-Thymocyte Globulin

Anti-Thymocyte Globulin 2.0 mg/kg/day x 4 days

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

No minimum to 55 Years

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

Design outcomes

Primary

Measure	Time frame	Description
Total Number of Subjects With a Complete Response (CR) Following Myeloablative Conditioning (MAC) and Autologous Stem Cell Transplantation (AutoSCT)	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.
Total Number of Subjects With a Disease Relapse or Progression Following MAC AutoSCT	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.
Total Number of Subjects With Partial Response or Stable Disease Following MAC AutoSCT	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

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

Countries

United States

Participant flow

Pre-assignment details

Out of the 30 enrolled subjects, only 23 subjects received both MAC and AutoSCT and Reduced Intensity Conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT). 7 subjects did not complete the transplantation and therefore were not included into data analysis.

Participants by arm

Arm	Count
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.	6
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.	17
Total	23

Baseline characteristics

Characteristic	Arm A - Family Donor	Arm B - Unrelated Cord Blood or Adult	Total
Age, Categorical <=18 years	4 Participants	13 Participants	17 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	2 Participants	4 Participants	6 Participants
Sex: Female, Male Female	1 Participants	7 Participants	8 Participants
Sex: Female, Male Male	5 Participants	10 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 6	6 / 17
other Total, other adverse events	0 / 6	0 / 17
serious Total, serious adverse events	0 / 6	0 / 17

Outcome results

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.