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

NCT02548468 | Withdrawn Phase 1 DMC

• 2 other identifiers: 15D.237JT 6812
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• Incidence of GVHD

  Up to 100 days post-transplant

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

  day -4

Secondary Outcomes (7)

• Myeloid engraftment rate

  Up to 6 months post-transplant

• Lymphoid engraftment rate

  Up to 6 months post-transplant

• Incidence of GVHD using tacrolimus and mycophenolate mofetil prophylaxis

  Up to 6 months post-transplant

• Progression free survival

  Up to 6 months post-transplant

• Overall survival (OS)

  Up to 6 months post-transplant

Study Arms (1)

Reduced Intensity Conditioning, DLI, PBSCT

EXPERIMENTAL

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.

Drug: Fludarabine; Radiation: Total-Body Irradiation; Biological: T Cell-Depleted Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Mycophenolate mofetil; Drug: Tacrolimus

Interventions

Fludarabine DRUG

Given IV

Also known as: Fludarabine phosphate, Fludara

Reduced Intensity Conditioning, DLI, PBSCT

Total-Body Irradiation RADIATION

Undergo TBI

Reduced Intensity Conditioning, DLI, PBSCT

T Cell-Depleted Donor Lymphocyte Infusion BIOLOGICAL

Undergo donor CD3+ enriched T lymphocyte infusion

Reduced Intensity Conditioning, DLI, PBSCT

Cyclophosphamide DRUG

Given IV

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin, Cytophosphane, CP

Reduced Intensity Conditioning, DLI, PBSCT

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic HSC transplant

Reduced Intensity Conditioning, DLI, PBSCT

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Reduced Intensity Conditioning, DLI, PBSCT

Mycophenolate mofetil DRUG

Given IV

Also known as: MMF

Reduced Intensity Conditioning, DLI, PBSCT

Tacrolimus DRUG

Given IV

Also known as: FK-506, Fujimycin, Prograf, Advagraf, Protopic

Reduced Intensity Conditioning, DLI, PBSCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Related Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Jefferson University Hospitals

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

fludarabine; fludarabine phosphate; Whole-Body Irradiation; Cyclophosphamide; Peripheral Blood Stem Cell Transplantation; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• S. Onder Alpdogan, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 14, 2015
• Study Start: November 20, 2015
• Primary Completion: January 23, 2017
• Study Completion: March 16, 2017
• Last Updated: May 2, 2025

Record last verified: 2025-05