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

Sponsor

Yale University (Other)

Overall Status

Completed

CT.gov ID

NCT00104975

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

38.9

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Biological: alemtuzumab Biological: therapeutic allogeneic lymphocytes Drug: fludarabine phosphate Drug: melphalan Drug: tacrolimus Drug: thiotepa Procedure: peripheral blood stem cell transplantation	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Primary Purpose:

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

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

May 1, 2008

Actual Study Completion Date :

May 1, 2008

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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