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Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
alemtuzumab
therapeutic allogeneic lymphocytes
fludarabine phosphate
melphalan
tacrolimus
thiotepa
peripheral blood stem cell transplantation
Sponsored by
Yale University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring accelerated phase chronic myelogenous leukemia, recurrent adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, secondary myelodysplastic syndromes, chronic myelomonocytic leukemia, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, primary myelofibrosis, chronic neutrophilic leukemia, essential thrombocythemia, polycythemia vera, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), recurrent adult acute myeloid leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult Burkitt lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, myelodysplastic/myeloproliferative neoplasm, unclassifiable, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Chronic myelogenous leukemia Accelerated phase or blast phase Acute myeloid leukemia, meeting any of the following criteria: In second or subsequent remission In primary induction failure In partial remission In resistant relapse Chronic lymphocytic leukemia In Richter's transformation High-grade non-Hodgkin's lymphoma Refractory to standard treatment Myeloproliferative disorders Undergoing transformation to terminal stages Myelodysplastic syndromes (MDS), including any of the following: Refractory anemia with excess blasts Transformation to acute leukemia MDS secondary to chemotherapy Partially-matched related family donor available One HLA haplotype match No HLA-matched (10/10 or 9/10) sibling donor or unrelated donor available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 18 to 55 Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Not specified Hepatic SGOT and SGPT < 3 times upper limit of normal (ULN) No active or persistent viral hepatitis Renal Creatinine < 2.0 mg/dL* OR Creatinine clearance > 60 mL/min* NOTE: *Unless due to malignancy Cardiovascular LVEF ≥ 45% Pulmonary DLCO ≥ 60% of predicted* (corrected for hemoglobin) NOTE: *Unless patient is given clearance by a pulmonary consultation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 2 years after completion of study treatment HIV negative Human T cell lymphotrophic virus type 1 negative No serious co-morbid medical condition No other medical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified

Sites / Locations

  • Yale Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 3, 2005
Last Updated
December 13, 2016
Sponsor
Yale University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00104975
Brief Title
Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Official Title
Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and after transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of donor lymphocytes when given after alemtuzumab and combination chemotherapy in treating patients who are undergoing donor stem cell transplant for hematologic cancer.
Detailed Description
OBJECTIVES: Determine the feasibility and efficacy of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies. Determine the toxicity of this regimen in these patients. Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells, administered after allogeneic PBSCT, in these patients. OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted donor T cells. T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order to selectively deplete T cells from the donor PBMCs. Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5, fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day -4, and thiotepa IV on days -3 to -2. Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1. Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic PBSC transplantation on day 0. LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2 immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on approximately day 28. Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated, selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting-toxicity. After completion of study treatment, patients are followed weekly for 100 days post-transplantation and then periodically for survival. PROJECTED ACCRUAL: A total of 15-20 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
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
accelerated phase chronic myelogenous leukemia, recurrent adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, secondary myelodysplastic syndromes, chronic myelomonocytic leukemia, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, primary myelofibrosis, chronic neutrophilic leukemia, essential thrombocythemia, polycythemia vera, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), recurrent adult acute myeloid leukemia, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III adult Burkitt lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, myelodysplastic/myeloproliferative neoplasm, unclassifiable, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
alemtuzumab
Intervention Type
Biological
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Chronic myelogenous leukemia Accelerated phase or blast phase Acute myeloid leukemia, meeting any of the following criteria: In second or subsequent remission In primary induction failure In partial remission In resistant relapse Chronic lymphocytic leukemia In Richter's transformation High-grade non-Hodgkin's lymphoma Refractory to standard treatment Myeloproliferative disorders Undergoing transformation to terminal stages Myelodysplastic syndromes (MDS), including any of the following: Refractory anemia with excess blasts Transformation to acute leukemia MDS secondary to chemotherapy Partially-matched related family donor available One HLA haplotype match No HLA-matched (10/10 or 9/10) sibling donor or unrelated donor available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 18 to 55 Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Not specified Hepatic SGOT and SGPT < 3 times upper limit of normal (ULN) No active or persistent viral hepatitis Renal Creatinine < 2.0 mg/dL* OR Creatinine clearance > 60 mL/min* NOTE: *Unless due to malignancy Cardiovascular LVEF ≥ 45% Pulmonary DLCO ≥ 60% of predicted* (corrected for hemoglobin) NOTE: *Unless patient is given clearance by a pulmonary consultation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for up to 2 years after completion of study treatment HIV negative Human T cell lymphotrophic virus type 1 negative No serious co-morbid medical condition No other medical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Erkut Bahceci, MD
Organizational Affiliation
Yale University
Official's Role
Study Chair
Facility Information:
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8028
Country
United States

12. IPD Sharing Statement

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Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

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