Autologous and Allogeneic Transplant for Relapsed Lymphoma

NCT ID: NCT00802113

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2014-10-22

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.

Conditions

Non-Hodgkin's Lymphoma; Hodgkins Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 x 5 days

Busulfan

Intervention Type: DRUG

Busulfan 3.2 mg/kg/day x 2 days

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.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 x 5 days

Busulfan

Intervention Type: DRUG

Busulfan 3.2 mg/kg/day x 2 days

Anti-Thymocyte Globulin

Intervention Type: DRUG

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

Interventions

Fludarabine

Fludarabine 30 mg/m2 x 5 days

Intervention Type: DRUG

Busulfan

Busulfan 3.2 mg/kg/day x 2 days

Intervention Type: DRUG

Anti-Thymocyte Globulin

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

Intervention Type: DRUG

Other Intervention Names

Fludara; Busulfex; ATG

Eligibility 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

• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Prakash Satwani

Assistant Professor of Clinical Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prakash Satwani, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Children's Memorial Hospital in Chicago

Chicago, Illinois, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University Medical Center

New York, New York, United States

New York Medical College

Valhalla, New York, United States

Duke University

Durham, North Carolina, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

CHNY-01-501

Identifier Type: OTHER

Identifier Source: secondary_id

AAAA5185

Identifier Type: -

Identifier Source: org_study_id