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

Primary Purpose

Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent Mycosis Fungoides and Sezary Syndrome, Stage IIB Mycosis Fungoides and Sezary Syndrome

Status

Withdrawn

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Fludarabine

Total-Body Irradiation

T Cell-Depleted Donor Lymphocyte Infusion

Cyclophosphamide

Allogeneic Hematopoietic Stem Cell Transplantation

Peripheral Blood Stem Cell Transplantation

Mycophenolate mofetil

Tacrolimus

About this trial

This is an interventional treatment trial for Cutaneous T-Cell Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Stage IIB-IV mycosis fungoides and sezary syndrome who have failed at least one standard systemic therapy or are not candidates for standard therapy.
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.
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.
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
Performance status > 80% (Karnofsky)
Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) <5 for age < 65, HCT-CI <4 for age >65
Patients must be willing to use contraception if they have childbearing potential
Able to give informed consent, or their legally authorized representative can give informed consent.

Exclusion Criteria:

Performance status of < 80% (Karnofsky)
HIV positive
Active involvement of the central nervous system with malignancy
Psychiatric disorder that would preclude patients from signing an informed consent
Pregnancy, or unwillingness to use contraception if they are have childbearing potential.
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder or complications there from.
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.
Patients who cannot receive cyclophosphamide
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.
Uncontrolled active infection

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reduced Intensity Conditioning, DLI, PBSCT

Arm Description

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -11 to -8 and undergo total body irradiation BID on day -7. Patients also receive donor CD3+ enriched T lymphocyte infusion on day -6 and high-dose cyclophosphamide IV over 2 hours on days -3 to -2. TRANSPLANT: Patients undergo allogeneic 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.

Outcomes

Primary Outcome Measures

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.

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.

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.

Incidence of GVHD

Maximum tolerated dose of DLI, determined according to dose limiting toxicities

Secondary Outcome Measures

Myeloid engraftment rate

Lymphoid engraftment rate

Incidence of GVHD using tacrolimus and mycophenolate mofetil prophylaxis

Progression free survival

Progression free survival will be estimated by the Kaplan-Meier method.

Overall survival (OS)

OS will be estimated by the Kaplan-Meier method.

Rate of lymphoid recovery

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.

Full Information

NCT ID

NCT02548468

First Posted

September 8, 2015

Last Updated

April 17, 2017

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

1. Study Identification

Unique Protocol Identification Number

NCT02548468

Brief Title

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

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Slow accrual

Study Start Date

November 20, 2015 (Actual)

Primary Completion Date

January 23, 2017 (Actual)

Study Completion Date

March 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Reduced Intensity Conditioning, DLI, PBSCT

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludarabine phosphate, Fludara

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Total-Body Irradiation

Intervention Description

Undergo TBI

Intervention Type

Biological

Intervention Name(s)

T Cell-Depleted Donor Lymphocyte Infusion

Intervention Description

Undergo donor CD3+ enriched T lymphocyte infusion

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin, Cytophosphane, CP

Intervention Description

Given IV

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Description

Undergo allogeneic HSC transplant

Intervention Type

Procedure

Intervention Name(s)

Peripheral Blood Stem Cell Transplantation

Intervention Description

Undergo allogeneic PBSCT

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

MMF

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

FK-506, Fujimycin, Prograf, Advagraf, Protopic

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Rate of regimen-related toxicities

Description

Time Frame

Up to 100 days post-transplant

Title

Rate for hematopoietic engraftment

Description

Time Frame

Up to 100 days post-transplant

Title

Rate for immune reconstitution

Description

Time Frame

Up to 100 days post-transplant

Title

Incidence of GVHD

Time Frame

Up to 100 days post-transplant

Title

Maximum tolerated dose of DLI, determined according to dose limiting toxicities

Time Frame

day -4

Secondary Outcome Measure Information:

Title

Myeloid engraftment rate

Time Frame