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

Sponsors and Collaborators:	Yale University National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00104975

Purpose

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.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: alemtuzumab Biological: therapeutic allogeneic lymphocytes Drug: fludarabine phosphate Drug: melphalan Drug: tacrolimus Drug: thiotepa Procedure: peripheral blood stem cell transplantation	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Thiotepa Fludarabine Fludarabine monophosphate Tacrolimus anhydrous Tacrolimus Campath Alemtuzumab Melphalan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
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

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	20
Study Start Date:	February 2005

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00104975

Locations

United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028

Sponsors and Collaborators

Yale University

National Cancer Institute (NCI)

Investigators

Study Chair:

Erkut Bahceci, MD

Yale University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000413698, YALE-25971, NCI-6765
Study First Received:	March 3, 2005
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00104975 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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
chronic idiopathic 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

Study placed in the following topic categories:

Polycythemia
Chronic Myelomonocytic Leukemia
Blast Crisis
Tacrolimus
Refractory Anemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Alemtuzumab
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Myelodysplastic Myeloproliferative Disease
Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myeloproliferative Disorders
Leukemia, Myeloid
Thiotepa
Leukemia, Myeloid, Accelerated Phase
Fludarabine
Chronic Myelogenous Leukemia
Antimetabolites
Melphalan
Leukemia, Lymphoid
Immunologic Factors
Hematologic Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Leukemia
Preleukemia
Pathologic Processes
Therapeutic Uses
Syndrome
Alemtuzumab
Lymphoma

Immunoproliferative Disorders
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine
Lymphoproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases

ClinicalTrials.gov processed this record on May 07, 2009