Phase 2 N=5 Treatment

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

Mycosis Fungoides · Sezary Syndrome

Bottom Line

View on ClinicalTrials.gov: NCT00047060 ↗

Enrolled (actual)

Serious AEs

100.0%

Results posted

Feb 2020

Primary outcome: Primary: Efficacy of Nonmyeloablative Preparative Regimen — 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: A matched peripheral donor stem cells (Other); cyclosporine (Drug); fludarabine (Drug); Campath (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Primary completion: Jan 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY Efficacy of Nonmyeloablative Preparative Regimen	4	—
SECONDARY Number of Participants Who Experienced Acute GVHD Grades II-IV	0; 1	—
SECONDARY Number of Participant Who Experienced Chronic Graft Versus Host Disease	3; 0	—
SECONDARY Number of Participants That Experienced Graft Failure	—	—
SECONDARY Overall Response	4; 1; 0; 0	—
SECONDARY Number of Participants Who Experienced Transplant Related Mortality	—	—
SECONDARY Number of Participants Overall Survival	3	—
SECONDARY Number of Participants That Remained Disease-free	4	—
SECONDARY Number of Participants That Experienced Engraftment	5	—
SECONDARY Number of Participants That Experienced Platelet Recovery	5	—
SECONDARY Number of Participants That Experienced Red Blood Cell Recovery	5	—
SECONDARY Median Time in Months to Achieve Full Myeloid and Full Donor T-cell Chimerism	9; 7	—

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.

Eligibility Criteria

INCLUSION CRITERIA-RECIPIENT:

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.

6/6 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.

INCLUSION CRITERIA-RELATED and UNRELATED DONOR:

6/6 HLA- matched family donor or 10/10 HLA-matched unrelated donor

Age greater than or equal to 18 years

Ability to comprehend the investigational nature of the study and provide informed consent.

For unrelated donor, the NMDP unrelated donor inclusion criteria will be used as outlined in document (http://bethematch.org/WorkArea/DownloadAsset.aspx?id=1960).

Donor eligibility will be completed per NMDP standards and in accordance with most recent and stringent FDA guidelines.

EXCLUSION CRITERIA (ANY OF THE FOLLOWING)-RECIPIENT

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.

EXCLUSION CRITERIA (any of the following)-RELATED AND UNRELATED DONOR:

Donor pregnant or lactating

Age less than 18 years

HIV positive (donors who are positive for hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-1) will be used at the discretion of the investigator following counseling and approval from the recipient).

Sickling hemoglobinopathy including HbSS or HbsC (for unrelated donors, testing for hemoglobinopathies will only be done when clinically indicated).

History of malignancy within 5 years except basal cell or squamous carcinoma of the skin.

Donor unfit to receive G-CSF and undergo apheresis (Uncontrolled hypertension, history of stroke, thrombocytopenia).

Psychiatric disorder or mental deficiency of the donor sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00047060). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.