Alemtuzumab Followed by Peripheral Stem Cell Transplantation in Treating Patients With Advanced Mycosis Fungoides/Sezary Syndrome - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00047060

Purpose

RATIONALE: Monoclonal antibodies such as alemtuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Allogeneic peripheral stem cell transplantation may be able to replace immune cells that were destroyed by the anticancer therapy. Sometimes the transplanted cells are rejected by the body's normal tissues. Mycophenolate mofetil and cyclosporine may prevent this rejection.

PURPOSE: This phase I/II trial is studying how well giving alemtuzumab together with chemotherapy and donor peripheral stem cell transplantation works in treating patients with advanced mycosis fungoides and/or Sezary syndrome.

Condition	Intervention	Phase
Lymphoma	Biological: alemtuzumab Drug: cyclophosphamide Drug: fludarabine phosphate	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Study Of HLA-Matched Mobilized Peripheral Blood Hematopoetic Stem Cell Transplantation For Advanced Mycosis Fungoides/Sezary Using NonMyeloablative Conditioning With Campath-1H

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fungal Infections Lymphoma

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Campath Alemtuzumab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Engraftment measured by donor-host chimerism in lymphoid and myeloid lines at days 15, 30, 45, 60, and 100 [ Designated as safety issue: No ]
Response (complete [CR] and partial responses [PR] and stable [SD] or progressive disease [PD]) at days 30, 60, and 100 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Immune reconstitution measured by lymphocyte subset analysis and T cell repertoire at days 15, 30, 45, 60, and 100 [ Designated as safety issue: No ]
Safety measured by incidence and severity of post-transplant complications [ Designated as safety issue: Yes ]

Estimated Enrollment:	58
Study Start Date:	July 2002
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen A: Experimental Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15 and fludarabine IV over 30 minutes on days -5 to -1.	Biological: alemtuzumab Given IV Drug: fludarabine phosphate Given IV
Regimen B: Experimental Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15; fludarabine IV over 30 minutes on days -5 to -1; and cyclophosphamide IV over 1 hour on days -7 and -6.	Biological: alemtuzumab Given IV Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV

Detailed Description:

OBJECTIVES:

Evaluate the ability of a conditioning regimen comprising alemtuzumab and fludarabine with or without cyclophosphamide to produce at least 80% sustained engraftment in patients with advanced mycosis fungoides/Sezary syndrome.
Evaluate allogeneic graft-versus-tumor effects in mycosis fungoides/Sezary syndrome patients treated with a nonmyeloablative conditioning regimen followed by HLA-matched allogeneic peripheral blood stem cell transplantation.
Determine the safety and toxicity of this regimen in these patients.
Determine tumor response, disease-free survival, and overall survival of patients treated with this regimen.
Determine the rate and extent of lymphocyte subset reconstitution in patients treated with this regimen.
Determine transplant-related morbidity, including rates of acute and chronic graft-versus-host disease and infectious complications, and mortality in patients treated with this regimen.

OUTLINE: Patients receive 1 of 2 nonmyeloablative conditioning regimens, depending on engraftment efficacy in prior patients.

Regimen A: Patients receive alemtuzumab IV over 2 hours on days -28, -27, -26, -24, -22, -19, -17, and -15 and fludarabine IV over 30 minutes on days -5 to -1.
Regimen B: Patients receive alemtuzumab and fludarabine as in regimen A plus cyclophosphamide IV over 1 hour on days -7 and -6.

Patients also receive graft-versus-host disease prophylaxis comprising oral cyclosporine twice a day beginning on day -4 and continuing until day 100.

Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.

Donor T cell and myeloid chimerism will be evaluated and will guide decisions regarding donor lymphocyte infusions.

Patients are followed every 2 months for 6 months, every 3 months for 1.5 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 9-58 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

One of the following diagnoses:
- Histologically confirmed mycosis fungoides (MF)
  - Stage IIB, III, IVA, or IVB
  - Progressive disease after at least 1 treatment regimen
- Sezary syndrome (SS)
Clinically or radiographically evaluable disease
Anticipated median survival of less than 5 years or debilitation as result of disease
Less than 25% of liver involved with metastatic tumor by CT scan
No CNS metastases by MRI
6/6 HLA-matched family donor available

PATIENT CHARACTERISTICS:

Age

18 to 70

Performance status

ECOG 0-1

Life expectancy

See Disease Characteristics
At least 3 months

Hematopoietic

Not specified

Hepatic

See Disease Characteristics
Bilirubin no greater than 4 mg/dL
Transaminases no greater than 5 times upper limit of normal

Renal

Creatinine no greater than 2 mg/dL

Cardiovascular

LVEF at least 40%

Pulmonary

DLCO at least 60% of predicted

Other

HIV negative
Not pregnant or nursing
Negative pregnancy test
No major organ dysfunction or failure or major anticipated illness that would preclude transplantation
No psychiatric disorder or mental deficiency that would preclude study
No other malignancy within the past 5 years except basal cell or squamous cell skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 30 days since prior therapy for MF or SS

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047060

Locations

United States, Maryland
NIH - Warren Grant Magnuson Clinical Center	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Patient Recruitment 800-411-1222

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Ramaprasad Srinivasan, MD

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	National Heart, Lung, and Blood Institute ( Ramaprasad Srinivasan )
Study ID Numbers:	CDR0000257524, NHLBI-02-H-0250
Study First Received:	October 3, 2002
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00047060 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Vidarabine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Sezary Syndrome
Mycosis Fungoides
Cyclophosphamide
Mycoses
Lymphoma, T-Cell
Alemtuzumab
Therapeutic Uses

Alkylating Agents
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on November 27, 2009