Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma

PRIMARY OBJECTVES:

I. To evaluate regimen related toxicity, engraftment and graft versus host disease (GVHD) in
the first 100 days with new reduced intensity haploidentical regimen protocol, including
fludarabine (fludarabine phosphate), low dose total body irradiation, and cyclophosphamide.

II. To determine an effective donor lymphocyte infusion (DLI) dose that provides successful
engraftment without causing GVHD.

SECONDARY OBJECTIVES:

I. To assess myeloid and lymphoid engraftment rates of patients undergoing treatment on this
regimen.

II. To determine the incidence and severity of GVHD in patients undergoing treatment on this
regimen using a combination of tacrolimus and mycophenolate mofetil (MMF) as GVHD
prophylaxis.

III. To examine progression free survival and overall survival in patients with cytotoxic
T-cell lymphoma (CTCL) undergoing treatment on this regimen.

IV. To assess the pace of lymphoid recovery in this patient population.

OUTLINE: This is a phase I, dose-escalation study of DLI.

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV)
over 30 minutes on days -11 to -8 and undergo total body irradiation twice daily (BID) on
day -7. Patients also receive donor cluster of differentiation (CD)3+ enriched T lymphocyte
infusion on day -6 and high-dose cyclophosphamide IV over 2 hours on days -3 to -2.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day
0.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV with taper (drug wean)
by day 60 and mycophenolate mofetil IV BID on days -1 to 28 in the absence of GVHD.

After completion of treatment, patients are followed up periodically.

Inclusion Criteria:

1. Stage IIB-IV mycosis fungoides and sezary syndrome who have failed at least one
standard systemic therapy or are not candidates for standard therapy.

2. Patient should have a responsive skin disease including complete remission (CR) and
partial remission (PR) (close to CR; 75%-99% clearance of skin disease from baseline
without new tumors (T3) in patients with T1, T2 or T4 only skin disease) and should
not have visceral organ or lymph node involvement prior to transplantation.

3. Patients must have a related donor who is a two or more allele mismatch at the HLA-A;
B; C; DR and DQ loci. Patients who have sibling donors with a one antigen mismatch
due to recombination will not be enrolled in this protocol.

4. Patients must have adequate organ function:

- Left Ventricular Ejection Fraction (LVEF) of >50%

- Carbon Monoxide Diffusing Capacity (DLCO) >50% of predicted corrected for
hemoglobin

- Adequate liver function as defined by a serum bilirubin <2.0 (unless hemolysis
or Gilbert disease), Aspartate aminotransferase (AST) or Alanine
aminotransferase (ALT) < 2.5 X upper limit of normal

- Creatinine clearance of > 60 ml/min

5. Performance status > 80% (Karnofsky)

6. Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) <5 for age <
65, HCT-CI <4 for age >65

7. Patients must be willing to use contraception if they have childbearing potential

8. Able to give informed consent, or their legally authorized representative can give
informed consent.

Exclusion Criteria:

1. Performance status of < 80% (Karnofsky)

2. HIV positive

3. Active involvement of the central nervous system with malignancy

4. Psychiatric disorder that would preclude patients from signing an informed consent

5. Pregnancy, or unwillingness to use contraception if they are have childbearing
potential.

6. Patients with life expectancy of < 6 months for reasons other than their underlying
hematologic/oncologic disorder or complications there from.

7. Patients who have received alemtuzumab within 8 weeks of transplant admission, or who
have recently received horse or rabbit anti-thymocyte globulin (ATG) and have ATG
levels of > 2 μgm/ml.

8. Patients who cannot receive cyclophosphamide

9. Patients with evidence of another malignancy (exclusive of a skin cancer that
requires only local treatment);

- Patients with prior malignancies diagnosed> 5 years ago without evidence of
disease are eligible.

- Patients with prior malignancy treated < 5 years ago but have a life expectancy
of > 5 years for that malignancy are eligible.

10. Uncontrolled active infection