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| Sponsor: | Fred Hutchinson Cancer Research Center |
|---|---|
| Collaborators: |
National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI) |
| Information provided by: | Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00040846 |
Purpose
This phase II trial studies the side effects and the best dose of alemtuzumab when given together with fludarabine phosphate and low-dose total body irradiation (TBI) and how well it works before donor stem cell transplant in treating patients with hematological malignancies. Giving chemotherapy and low-dose TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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 also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after transplant may stop this from happening
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Burkitt Lymphoma Childhood Chronic Myelogenous Leukemia Childhood Diffuse Large Cell Lymphoma Childhood Immunoblastic Large Cell Lymphoma Childhood Nasal Type Extranodal NK/T-cell Lymphoma Chronic Phase Chronic Myelogenous Leukemia Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Peripheral T-cell Lymphoma Previously Treated Myelodysplastic Syndromes Progressive Hairy Cell Leukemia, Initial Treatment Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Splenic Marginal Zone Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Childhood Anaplastic Large Cell Lymphoma Stage I Childhood Large Cell Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Mycosis Fungoides/Sezary Syndrome Stage I Small Lymphocytic Lymphoma Stage II Childhood Anaplastic Large Cell Lymphoma Stage II Childhood Large Cell Lymphoma Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Mycosis Fungoides/Sezary Syndrome Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Childhood Anaplastic Large Cell Lymphoma Stage III Childhood Large Cell Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Childhood Anaplastic Large Cell Lymphoma Stage IV Childhood Large Cell Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma T-cell Large Granular Lymphocyte Leukemia Waldenstrom Macroglobulinemia |
Biological: alemtuzumab Drug: fludarabine phosphate Radiation: total-body irradiation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Drug: mycophenolate mofetil Drug: cyclosporine |
Phase II |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Campath® [Alemtuzumab] Dose Escalation, Low-Dose TBI and Fludarabine Followed by HLA Class I Mismatched Donor Stem Cell Transplantation for Patients With Hematologic Malignancies - A Multi-Center Trial |
| Estimated Enrollment: | 60 |
| Study Start Date: | November 2001 |
| Estimated Study Completion Date: | December 2013 |
| Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (dose-escalation of alemtuzumab, HSCT)
CONDITIONING REGIMEN: Patients receive alemtuzumab IV over 2 hours on days -8 to -5 and fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0. HSCT: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. IMMUNOSUPPRESSION: Patients receive CSP IV or PO BID on days -3 to 180 with taper to day 365 and MMF PO TID on days 0-100, with taper to day 156. |
Biological: alemtuzumab
Given IV
Other Names:
Drug: fludarabine phosphate
Given IV
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic HSCT
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplantation
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Drug: cyclosporine
Given IV or PO
Other Names:
|
PRIMARY OBJECTIVES:
I. To determine whether stable allogeneic engraftment from related and unrelated human leukocyte antigen (HLA)-mismatched stem cell donors can be safely established using a non-myeloablative conditioning regimen plus escalating doses of the anti-CD52 monoclonal antibody (mAb) Campath (alemtuzumab) in patients with hematologic malignancies.
SECONDARY OBJECTIVES:
I. Evaluate the risk of occurrence of acute and chronic graft-vs-host disease (GVHD).
II. Evaluate the risk/incidence of infections. III. Determine whether engraftment can be maintained with a single dose fludarabine, donor lymphocyte infusion (DLI) and continued MMF/CSP.
IV. Evaluate the risk for disease progression and relapse.
OUTLINE: This is a dose-escalation study of alemtuzumab.
CONDITIONING REGIMEN: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -5 and fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0.
HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive CSP IV or orally (PO) twice daily (BID) on days -3 to 180 with taper to day 365 and MMF PO thrice daily (TID) on days 0-100 with taper to day 156.
After completion of study treatment, patients are followed up periodically.
Eligibility| Ages Eligible for Study: | up to 74 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| United States, Colorado | |
| Presbyterian - Saint Lukes Medical Center - Health One | |
| Denver, Colorado, United States, 80218 | |
| United States, Utah | |
| University of Utah | |
| Salt Lake City, Utah, United States, 84112 | |
| LDS Hospital | |
| Salt Lake City, Utah, United States, 84143 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| VA Puget Sound Health Care System | |
| Seattle, Washington, United States, 98101 | |
| Italy | |
| University of Torino | |
| Torino, Italy, 10126 | |
| Principal Investigator: | Brenda Sandmaier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
| Responsible Party: | Sandmaier, Brenda, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00040846 History of Changes |
| Other Study ID Numbers: | 1591.00, NCI-2011-00471, P01HL036444, P01CA018029 |
| Study First Received: | July 8, 2002 |
| Last Updated: | August 15, 2011 |
| Health Authority: | United States: Food and Drug Administration |
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Congenital Abnormalities Burkitt Lymphoma Neoplasms Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Hairy Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Leukemia, T-Cell |
Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Waldenstrom Macroglobulinemia Multiple Myeloma Neoplasms, Plasma Cell Mycoses Mycosis Fungoides Myelodysplastic Syndromes Preleukemia Myeloproliferative Disorders Sezary Syndrome |