Allogeneic Peripheral Stem Cell Transplantation Followed By Donor Lymphocyte Infusions in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed By T Cell Add-Back For Hematological Malignancies - Effect Of Irradiated Donor Lymphocytes On Chimerism

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00066300
• Other study ID #: CDR0000315460
• Secondary ID: NHLBI-03-H-0192
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 6, 2003
• Last updated: May 14, 2011
• Start date: May 2003

Study information

• Verified date: April 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening. Infusions of donor lymphocytes may decrease the body's rejection of the transplanted peripheral stem cells.

PURPOSE: Phase II trial to study the effectiveness of allogeneic stem cell transplantation followed by donor lymphocyte infusions in treating patients who have hematologic cancer.

Description:

OBJECTIVES:

• Determine the effect of irradiated donor T-cell infusion on donor T-cell chimerism 6 weeks after hematopoietic stem cell transplantation in patients with hematologic malignancies.

• Determine the infusional toxic effects of irradiated donor lymphocytes in these patients.

• Determine the risk of acute and chronic graft-versus-host disease from donor lymphocyte infusions on day 45 and day 100 posttransplantation in HLA 6/6 matched transplantations from a related donor in these patients.

• Determine disease-free survival, cytomegalovirus reactivation, and relapse in patients treated with this regimen.

• Determine transplant-related mortality and death from all causes in patients treated with this regimen.

OUTLINE:

• Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Patients undergo total body irradiation on days -7 to -4.

• Pretransplantation irradiated donor lymphocyte infusion (DLI): Patients receive irradiated DLI on day -4.

• Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.

• Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine on days 44-120.

• Posttransplantation DLI: Patients receive DLI on days 45 and 100. Patients with chronic myelogenous leukemia in chronic phase who are polymerase chain reaction negative for bcr/abl receive DLI on day 45 only.

Patients are followed at 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Other known NCT identifiers

• NCT00061581

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 55 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of any of the following hematologic malignancies:

• Chronic myelogenous leukemia (CML) in chronic phase meeting 1 of the following criteria:

• Under 41 years of age with no prior imatinib mesylate therapy

• 10 to 55 years of age and failed prior imatinib mesylate therapy

• 41 to 55 years of age for whom imatinib mesylate is not the treatment of choice

• CML in accelerated phase or blast transformation

• Acute lymphoblastic leukemia meeting any of the following criteria:

• Over 18 years of age and in first remission with high-risk features (e.g., WBC greater than 100,000/mm^3, karyotypes t[9;22], t[4], t[19], t[11], and biphenotypic leukemia)

• Second or subsequent remission

• Primary induction failure

• Partially responding or untreated relapse

• Acute myeloid leukemia meeting any of the following criteria:

• First remission, except with good-risk karyotypes (e.g., M3 t[15;17], M4E0 inv[16], t[8;21])

• Second or subsequent remission

• Primary induction failure

• Resistant relapse

• Myelodysplastic syndromes of any of the following types:

• Refractory anemia (RA) with transfusion dependence

• RA with excess blasts

• In transformation to acute leukemia

• Chronic myelomonocytic leukemia

• Myeloproliferative disorders in transformation to acute leukemia, of any of the following types:

• Myelofibrosis

• Polycythemia vera

• Essential thrombocythemia

• Chronic lymphocytic leukemia that is refractory to fludarabine with 1 of the following:

• Bulky progressive disease

• Thrombocytopenia (WBC no greater than 100,000/mm^3)*

• Anemia (hemoglobin no greater than 10 g/dL)* NOTE: *Not due to recent chemotherapy

• Non-Hodgkin's lymphoma, including mantle cell lymphoma, relapsing or refractory to current chemotherapy and monoclonal antibody therapy and unsuitable for autologous stem cell transplantation

• Availability of a HLA-identical (6/6) family donor

PATIENT CHARACTERISTICS:

Age

• 10 to 55

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 4 mg/dL

• Transaminases no greater than 3 times upper limit of normal

Renal

• Creatinine no greater than 3 mg/dL

Cardiovascular

• LVEF at least 40% of predicted

Pulmonary

• DLCO at least 60% of predicted

Other

• Not pregnant

• Negative pregnancy test

• HIV negative

• No severe psychiatric illness or mental deficiency that would preclude giving informed consent or complying with study treatment

• No major illness or organ dysfunction that would preclude transplantation

• No other prior malignancy except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

• No prior continuous busulfan for more than 6 months duration

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia

Intervention

Biological:
• graft-versus-tumor induction therapy

• therapeutic allogeneic lymphocytes

Drug:
• cyclophosphamide

• cyclosporine

• fludarabine phosphate

Procedure:
• allogeneic bone marrow transplantation

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States,