Allogeneic Peripheral Stem Cell Transplantation Followed By Donor Lymphocyte Infusions in Treating Patients With Hematologic Cancer
Recruitment status was Active, not recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms |
Biological: graft-versus-tumor induction therapy Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| 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 |
| Study Start Date: | May 2003 |
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.
Eligibility| Ages Eligible for Study: | 10 Years to 55 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Maryland | |
| Warren Grant Magnuson Clinical Center | |
| Bethesda, Maryland, United States, 20892-1182 | |
| Study Chair: | Austin J. Barrett, MD, FRCP | NHLBI - Bone Marrow Transplantation Unit |
More Information
Additional Information:
No publications provided by National Cancer Institute (NCI)
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| ClinicalTrials.gov Identifier: | NCT00066300 History of Changes |
| Obsolete Identifiers: | NCT00061581 |
| Other Study ID Numbers: | CDR0000315460, NHLBI-03-H-0192 |
| Study First Received: | August 6, 2003 |
| Last Updated: | May 14, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
chronic phase chronic myelogenous leukemia accelerated phase chronic myelogenous leukemia blastic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia primary myelofibrosis polycythemia vera essential thrombocythemia adult acute lymphoblastic leukemia in remission recurrent adult acute lymphoblastic leukemia adult acute myeloid leukemia in remission recurrent adult acute myeloid leukemia refractory chronic lymphocytic leukemia recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult Burkitt lymphoma |
recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma refractory anemia with excess blasts in transformation refractory anemia with excess blasts chronic myelomonocytic leukemia refractory anemia childhood acute lymphoblastic leukemia in remission childhood acute myeloid leukemia in remission recurrent childhood acute lymphoblastic leukemia recurrent childhood acute myeloid leukemia previously treated myelodysplastic syndromes secondary myelodysplastic syndromes de novo myelodysplastic syndromes |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Lymphoma Myelodysplastic Syndromes Preleukemia Myeloproliferative Disorders Myelodysplastic-Myeloproliferative Diseases Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |
Cyclophosphamide Cyclosporins Cyclosporine Fludarabine monophosphate Fludarabine Vidarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 18, 2013