Stem Cell Transplant Therapy With Campath-1H for Treating Advanced Mycosis Fungoides and Sezary Syndrome

NCT00047060 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 02025002-H-0250
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the safety and effectiveness of a modified donor stem cell transplantation procedure for treating advanced mycosis fungoides (MF), a lymphoma primarily affecting the skin, and Sezary syndrome (SS), a leukemic form of the disease. Donated stem cells (cells produced by the bone marrow that mature into the different blood components white cells, red cells and platelets) can cure patients with certain leukemias and lymphomas and multiple myeloma. These cells generate a completely new, functioning bone marrow. In addition, immune cells from the donor grow and generate a new immune system to help fight infections. The new immune cells also attack any residual tumor cells left in the body after intensive chemotherapy. However, stem cell transplantation carries a significant risk of death, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes from the donor may cause what is called graft vs. host disease (GvHD), in which these cells see the patient s cells as foreign and mount an immune response to destroy them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. In addition, a monoclonal antibody called Campath-1H will be given to target lymphocytes, including those that have become cancerous. Patients with advanced MF or SS who are between 18 and 70 years of age and have a matched family donor 18 years of age or older may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays of the chest, eye examination, and bone marrow sampling (withdrawal through a needle of about a tablespoon of marrow from the hip bone), and small skin biopsy (surgical removal of a piece of tissue for microscopic examination) or needle biopsy of the tumor. Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to push stem cells out of the bone marrow into the bloodstream. Then, the stem cells will be collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed. The rest of the blood is returned through a needle in the other arm. Before the transplant, a central venous line (large plastic tube) is placed into a major vein. This tube can stay in the body and be used the entire treatment period to deliver the donated stem cells, give medications, transfuse blood, if needed, and withdraw blood samples. Several days before the transplant procedure, patients will start a conditioning regimen of low-dose chemotherapy with Campath 1H, fludarabine, and, if necessary, cyclophosphamide. When the conditioning therapy is completed, the stem cells will be infused over a period of up to 4 hours. To help prevent rejection of donor cells and GvHD, cyclosporine and mycophenolate mofetil will be given by mouth or by vein for about 3 months starting 4 days before the transplantation. The anticipated hospital stay is 3 to 4 days, when the first 3 doses of Campath will be monitored for drug side effects. The rest of the procedures, including the transplant, can be done on an outpatient basis. Follow-up visits for the first 3 months after the transplant will be scheduled once or twice a week for a physical examination, blood tests and symptoms check. Then, visits will be scheduled at 6, 12, 18, 24, 30, 36, and 48 months post-transplant. Visits for the first 3 years will include blood tests, skin biopsies, and bone marrow biopsies.

Conditions

Mycosis Fungoides; Sezary Syndrome

Keywords

Cutaneous T Cell Lymphoma; Allogeneic PBSCT; Low Intensity Regimen; Mycosis Fungoides; Sezary Syndrome; CTCL

Outcome Measures

Primary Outcomes (1)

• Efficacy of Nonmyeloablative Preparative Regimen

  Proportion of subjects achieving a complete response. Complete response (CR) is defined as: disappearance of all signs and symptoms of cutaneous T-cell lymphomas (CTCL) for a period of at least one month.

  36 months

Secondary Outcomes (11)

• Number of Participants Who Experienced Acute GVHD Grades II-IV

  up to 100 days

• Number of Participant Who Experienced Chronic Graft Versus Host Disease

  Day 100 up to 3 years

• Number of Participants That Experienced Graft Failure

  up to 100 days

• Overall Response

  Up to 3 years

• Number of Participants Who Experienced Transplant Related Mortality

  day 100

Study Arms (1)

Stem Cell Transplant Therapy With Campath-1H

EXPERIMENTAL

Recipients received a nonmyeloablative preparative regimen of alemtuzumab 30mg iv three times a week for two weeks followed by fludarabine 25mg/m2/day for five days followed by a PBPC graft targeted to deliver ≥ 5x106 CD34+ cells/kg. Cyclosporine A (CSA) for GVHD prophylaxis used initially with target CSA levels in the therapeutic range (200 -400 ng/ml).

Other: A matched peripheral donor stem cells; Drug: cyclosporine; Drug: fludarabine; Drug: Campath

Interventions

A matched peripheral donor stem cells OTHER

A matched peripheral donor stem cells

Also known as: Allogeneic peripheral stem cell transplant

Stem Cell Transplant Therapy With Campath-1H

cyclosporine DRUG

cyclosporine

Also known as: CSA

Stem Cell Transplant Therapy With Campath-1H

fludarabine DRUG

fludarabine

Also known as: fludara

Stem Cell Transplant Therapy With Campath-1H

Campath DRUG

Campath

Also known as: Alemtuzumab

Stem Cell Transplant Therapy With Campath-1H

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18-70 years (both inclusive)
• Stages IIb to IVb patients with MF (biopsy diagnostic or consistent with MF) who have progressed despite at least one treatment regimen and all patients with SS
• AND
• Anticipated median survival less than 5 years or debilitation as a result of their disease.
• Recovery from acute toxicity of prior treatment for MF/SS (to less than or equal to grade 1 \[CTCAE v3.0\]) or stabilization of toxicity occurring from prior therapy for MF/SS.
• HIV negative
• ECOG performance status of 1 or less.
• No major organ dysfunction precluding transplantation.
• DLCO greater than or equal to 60 percent predicted
• Left ventricular ejection fraction greater than or equal to 40 percent.
• Less than or equal to 25 percent of liver involved with metastatic tumor by CT scan.
• /6 HLA matched family donor or 10/10 matched unrelated donor at the allelic level available
• Ability to comprehend the investigational nature of the study and provide informed consent.
• /6 HLA- matched family donor or 10/10 HLA-matched unrelated donor
• Age greater than or equal to 18 years

You may not qualify if:

• Patient pregnant or lactating
• Age greater than 70 or less than 18 years
• ECOG performance status of 2 or more.
• Psychiatric disorder or mental deficiency of the recipient or donor sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.
• Major anticipated illness or organ failure incompatible with survival from BMT and where survival is considered insufficient to assess transplant outcome (i.e. less than 3 months).
• DLCO less than 60 percent predicted
• Left ventricular ejection fraction less than 40 percent
• Serum creatinine greater than 2.0 mg/dl
• Serum bilirubin greater than 4 mg/dl, transaminases greater than 5 times the upper limit of normal
• HIV positive
• History of other malignancies in the last five years with the exception of basal cell or squamous cell carcinoma of the skin
• Evidence for CNS metastatic disease
• Disease involving greater than 25 percent of the liver radiographically.
• Donor pregnant or lactating
• Age less than 18 years

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Siegel RS, Pandolfino T, Guitart J, Rosen S, Kuzel TM. Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol. 2000 Aug;18(15):2908-25. doi: 10.1200/JCO.2000.18.15.2908.

  PMID: 10920140 BACKGROUND

• Diamandidou E, Cohen PR, Kurzrock R. Mycosis fungoides and Sezary syndrome. Blood. 1996 Oct 1;88(7):2385-409. No abstract available.

  PMID: 8839829 BACKGROUND

• Rook AH, Heald P. The immunopathogenesis of cutaneous T-cell lymphoma. Hematol Oncol Clin North Am. 1995 Oct;9(5):997-1010.

  PMID: 8522492 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

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

Interventions

Cyclosporine; fludarabine; fludarabine phosphate; Alemtuzumab

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)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Aue, Georg
• Organization: National Heart Lung and Blood Institute

aueg@nhlbi.nih.gov

+1 301 451 7141

Study Officials

• Georg Aue, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 3, 2002
• First Posted: January 27, 2003
• Study Start: July 30, 2002
• Primary Completion: January 24, 2019
• Study Completion: January 24, 2019
• Last Updated: November 14, 2023
• Results First Posted: February 24, 2020

Record last verified: 2019-02-13

Locations

US (1)