search
Back to results

Donor Stem Cell Transplant Followed By Donor White Blood Cell Infusions in Treating Young Patients With Hematologic Cancer

Primary Purpose

Leukemia, Lymphoma

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
therapeutic allogeneic lymphocytes
cyclosporine
fludarabine phosphate
melphalan
methotrexate
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent childhood small noncleaved cell lymphoma, juvenile myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent/refractory childhood Hodgkin lymphoma, childhood chronic myelogenous leukemia

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of one of the following hematopoietic malignancies: Acute lymphoblastic leukemia or myeloid leukemia with < 30% blasts in the bone marrow Juvenile myelomonocytic leukemia Chronic myelogenous leukemia in chronic or accelerated phase Relapsed non-Hodgkin's or Hodgkin's lymphoma in at least partial remission Considered at high risk (> 30%) of toxic death with standard hematopoietic stem cell transplantation (HSCT), as indicated by at least one of the following: Creatinine > 1.5 times normal OR creatinine clearance < 70 mL/min OR tubular damage that is not corrected by cessation of chemotherapy DLCO < 60% of predicted OR history of prior intubation due to lung disease (intubation for surgery excluded) Shortening fraction < 30% History of disseminated fungal infection during chemotherapy OR currently receiving antifungal agents OR history of ≥ 2 septic episodes (confirmed by cultures) that required ICU support Patients with improving fungal or other infections eligible Improving infection is defined as confirmed negative cultures on 2 separate occasions, at least 1 week apart, and/or stable or improving imaging studies (e.g., CT scan) of the infected site Two imaging studies taken at least 2 weeks apart must show stable or improved disease History of stroke or abnormal MRI/MRA OR leukoencephalopathy OR seizures that are not fully controlled with anticonvulsants (> 2 episodes of seizures in the preceding year or 1 episode of status epilepticus in a patient who is receiving anticonvulsant therapy) History of prior significant bleeding (e.g., pulmonary, CNS, or gastrointestinal) OR history of a clotting disorder as manifested by prior significant thromboses (e.g., superior vena cava, inferior vena cava, or femoral vein) Failed conventional therapies and not eligible for myeloablative protocols May have failed prior conventional HSCT No active CNS leukemia Unrelated or related donor available, meeting the following criteria: Matched for at least 7/8 loci by high-resolution typing One mismatch at A, B, or C loci allowed Fully matched at DRB1 locus PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% No active/progressing viral, bacterial, protozoal, or fungal infection Transaminases ≤ 5 times normal (except in the presence of autoimmune liver disease) Shortening fraction ≥ 25% DLCO ≥ 40% OR pulse oximetry ≥ 85% on room air Glomerular filtration rate ≥ 40 mL/min PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior prolonged intensive chemotherapy (> 3 years of therapy or ≥ 3 different chemotherapeutic protocols) allowed

Sites / Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 9, 2006
Last Updated
July 11, 2013
Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00301860
Brief Title
Donor Stem Cell Transplant Followed By Donor White Blood Cell Infusions in Treating Young Patients With Hematologic Cancer
Official Title
Feasibility of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation Followed by Donor Lymphocyte Infusions for Children at High Risk for Complications With Conventional Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Why Stopped
lack of efficacy
Study Start Date
January 2003 (undefined)
Primary Completion Date
March 2007 (Actual)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving chemotherapy, such as fludarabine and melphalan, and antithymocyte globulin before transplant and cyclosporine and methotrexate after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well donor stem cell transplant, using low-dose chemotherapy and antithymocyte globulin, followed by donor white blood cell infusions work in treating young patients with hematologic cancer.
Detailed Description
OBJECTIVES: Determine the feasibility of allogeneic hematopoietic stem cell transplantation using a reduced-intensity conditioning regimen, in terms of whole blood engraftment rate at 100 days post transplant, in pediatric patients with hematopoietic malignancies who are at high risk for complications with conventional transplantation. Determine the feasibility of donor lymphocyte infusions (DLIs), in terms of number of patients who receive at least one DLI by 12 months post transplant, in patients treated with this regimen. Determine the toxicities of the conditioning regimen, in terms of 100-day post transplant nonrelapse-related death rate, in these patients. Determine the toxicity of DLI, in terms of acute and chronic graft-vs-host disease rate and 12-month post transplant nonrelapse-related death rate, in these patients. OUTLINE: This is a pilot study. Reduced-intensity conditioning regimen: Patients receive fludarabine IV on days -6 to -2; antithymocyte globulin IV on days -5 to -2; and melphalan IV on days -3 and -2. Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 5 and continuing until blood counts recover. Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally beginning on day -1 and continuing until at least day 28 and methotrexate IV on days 1, 3, and 6. Donor lymphocyte infusion (DLI): Patients with mixed chimerism, no acute GVHD requiring therapy, and no relapse/progression post transplant at day 90 may receive DLI. At least 30 days after discontinuation of immunosuppression, patients may receive up to 2 DLIs at least 8-12 weeks apart in the absence of GVHD. At the completion of study treatment, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent childhood small noncleaved cell lymphoma, juvenile myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent/refractory childhood Hodgkin lymphoma, childhood chronic myelogenous leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of one of the following hematopoietic malignancies: Acute lymphoblastic leukemia or myeloid leukemia with < 30% blasts in the bone marrow Juvenile myelomonocytic leukemia Chronic myelogenous leukemia in chronic or accelerated phase Relapsed non-Hodgkin's or Hodgkin's lymphoma in at least partial remission Considered at high risk (> 30%) of toxic death with standard hematopoietic stem cell transplantation (HSCT), as indicated by at least one of the following: Creatinine > 1.5 times normal OR creatinine clearance < 70 mL/min OR tubular damage that is not corrected by cessation of chemotherapy DLCO < 60% of predicted OR history of prior intubation due to lung disease (intubation for surgery excluded) Shortening fraction < 30% History of disseminated fungal infection during chemotherapy OR currently receiving antifungal agents OR history of ≥ 2 septic episodes (confirmed by cultures) that required ICU support Patients with improving fungal or other infections eligible Improving infection is defined as confirmed negative cultures on 2 separate occasions, at least 1 week apart, and/or stable or improving imaging studies (e.g., CT scan) of the infected site Two imaging studies taken at least 2 weeks apart must show stable or improved disease History of stroke or abnormal MRI/MRA OR leukoencephalopathy OR seizures that are not fully controlled with anticonvulsants (> 2 episodes of seizures in the preceding year or 1 episode of status epilepticus in a patient who is receiving anticonvulsant therapy) History of prior significant bleeding (e.g., pulmonary, CNS, or gastrointestinal) OR history of a clotting disorder as manifested by prior significant thromboses (e.g., superior vena cava, inferior vena cava, or femoral vein) Failed conventional therapies and not eligible for myeloablative protocols May have failed prior conventional HSCT No active CNS leukemia Unrelated or related donor available, meeting the following criteria: Matched for at least 7/8 loci by high-resolution typing One mismatch at A, B, or C loci allowed Fully matched at DRB1 locus PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% No active/progressing viral, bacterial, protozoal, or fungal infection Transaminases ≤ 5 times normal (except in the presence of autoimmune liver disease) Shortening fraction ≥ 25% DLCO ≥ 40% OR pulse oximetry ≥ 85% on room air Glomerular filtration rate ≥ 40 mL/min PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior prolonged intensive chemotherapy (> 3 years of therapy or ≥ 3 different chemotherapeutic protocols) allowed
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Biljana Horn, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
Facility Information:
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Donor Stem Cell Transplant Followed By Donor White Blood Cell Infusions in Treating Young Patients With Hematologic Cancer

We'll reach out to this number within 24 hrs