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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT02548468
Other study ID # 15D.237
Secondary ID
Status Withdrawn
Phase Phase 1
First received September 8, 2015
Last updated April 17, 2017
Start date November 20, 2015
Est. completion date March 16, 2017

Study information

Verified date April 2017
Source Thomas Jefferson University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date March 16, 2017
Est. primary completion date January 23, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Fludarabine
Given IV
Radiation:
Total-Body Irradiation
Undergo TBI
Biological:
T Cell-Depleted Donor Lymphocyte Infusion
Undergo donor CD3+ enriched T lymphocyte infusion
Drug:
Cyclophosphamide
Given IV
Procedure:
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSC transplant
Peripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSCT
Drug:
Mycophenolate mofetil
Given IV
Tacrolimus
Given IV

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Sidney Kimmel Cancer Center at Thomas Jefferson University

Outcome

Type Measure Description Time frame Safety issue
Primary Rate of regimen-related toxicities Estimate of dose-specific rates of toxicity will be presented with corresponding confidence intervals using the exact method. The method of Atkinson and Brown will be used for any rate related to definition of dose limiting toxicity, due to two-stage sampling. Up to 100 days post-transplant
Primary Rate for hematopoietic engraftment Estimate of dose-specific rate for engraftment will be presented with corresponding confidence intervals using the exact method. The method of Atkinson and Brown will be used for any rate related to definition of dose limiting toxicity, due to two-stage sampling. Up to 100 days post-transplant
Primary Rate for immune reconstitution Estimate of dose-specific rate for immune reconstitution will be presented with corresponding confidence intervals using the exact method. The method of Atkinson and Brown will be used for any rate related to definition of dose limiting toxicity, due to two-stage sampling. Up to 100 days post-transplant
Primary Incidence of GVHD Up to 100 days post-transplant
Primary Maximum tolerated dose of DLI, determined according to dose limiting toxicities day -4
Secondary Myeloid engraftment rate Up to 6 months post-transplant
Secondary Lymphoid engraftment rate Up to 6 months post-transplant
Secondary Incidence of GVHD using tacrolimus and mycophenolate mofetil prophylaxis Up to 6 months post-transplant
Secondary Progression free survival Progression free survival will be estimated by the Kaplan-Meier method. Up to 6 months post-transplant
Secondary Overall survival (OS) OS will be estimated by the Kaplan-Meier method. Up to 6 months post-transplant
Secondary Rate of lymphoid recovery Up to 6 months post-transplant
Secondary Incidence of adverse events All estimates of dose-specific rates (e.g., toxicity) will be presented with corresponding confidence intervals using the exact method. The method of Atkinson and Brown will be used for any rate related to definition of dose limiting toxicity, due to two-stage sampling. Up to 6 months
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