Clinical trial NCT02548468: Reduced Intensity Conditioning Before Partially Matched Donor Stem Cell Transplant in Treating Patients With Advanced Cutaneous T Cell Lymphoma
Official title: A Two-Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Cutaneous T Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Cutaneous T-Cell Non-Hodgkin Lymphoma
Recurrent Mycosis Fungoides and Sezary Syndrome
Stage IIB Mycosis Fungoides and Sezary Syndrome
Stage IIIA Mycosis Fungoides and Sezary Syndrome
Stage IIIB Mycosis Fungoides and Sezary Syndrome
Stage IVA Mycosis Fungoides and Sezary Syndrome
Stage IVB Mycosis Fungoides and Sezary Syndrome
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
First posted: 2015-09-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial studies the side effects and the best dose of donor lymphocyte infusion when given together with reduced intensity conditioning regimen before partially matched donor stem cell transplant in treating patients with stage IIB-IV mycosis fungoides or Sezary syndrome. Giving chemotherapy and low-dose total-body irradiation followed by high-dose cyclophosphamide before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing the T-cells from the donor cells and giving them before transplant may stop this from happening. Additionally, giving tacrolimus and mycophenolate mofetil before and after transplant may also stop this from happening.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of regimen-related toxicities
timeFrame: Up to 100 days post-transplant
measure: Rate for hematopoietic engraftment
timeFrame: Up to 100 days post-transplant
measure: Rate for immune reconstitution
timeFrame: Up to 100 days post-transplant
measure: Incidence of GVHD
timeFrame: Up to 100 days post-transplant
measure: Maximum tolerated dose of DLI, determined according to dose limiting toxicities
timeFrame: day -4
Secondary outcomes:
measure: Myeloid engraftment rate
timeFrame: Up to 6 months post-transplant
measure: Lymphoid engraftment rate
timeFrame: Up to 6 months post-transplant
measure: Incidence of GVHD using tacrolimus and mycophenolate mofetil prophylaxis
timeFrame: Up to 6 months post-transplant
measure: Progression free survival
timeFrame: Up to 6 months post-transplant
measure: Overall survival (OS)
timeFrame: Up to 6 months post-transplant
measure: Rate of lymphoid recovery
timeFrame: Up to 6 months post-transplant
measure: Incidence of adverse events
timeFrame: Up to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Thomas Jefferson University
name: S. Onder Alpdogan, MD
role: PRINCIPAL_INVESTIGATOR
References: