Alemtuzumab, Fludarabine, Melphalan, and a Donor Stem Cell Transplant in Treating Young Patients With Resistant Langerhans Cell Histiocytosis - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00618540

Purpose

RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.

Condition	Intervention	Phase
Langerhans Cell Histiocytosis	Drug: alemtuzumab Drug: fludarabine phosphate Drug: melphalan Drug: therapeutic allogeneic lymphocytes Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation	Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer

Drug Information available for: Melphalan Fludarabine Fludarabine monophosphate Alemtuzumab Melphalan hydrochloride Sarcolysin Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

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

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Disease-free survival at 12 months post transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Transplantation-related mortality at day 100 [ Designated as safety issue: No ]
Relapse [ Designated as safety issue: No ]
Hematopoietic recovery and chimerism at day 100 and at 1 year post transplantation [ Designated as safety issue: No ]
Neutrophil and platelet engraftment [ Designated as safety issue: No ]
Incidence of grades II-IV and III-IV acute graft-versus-host-disease (GVHD) [ Designated as safety issue: No ]
Incidence of chronic GVHD [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	January 2007
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).

Secondary

To determine day 100 transplantation-related mortality.
To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
To determine the incidence of chronic GVHD.

OUTLINE: This is a multicenter study.

Non-myeloablative conditioning: Patients receive alemtuzumab IV over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab.
Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing to day 30 or 7 days after engraftment, whichever day is later, in the absence of GVHD. In patients with acute GVHD requiring systemic therapy, MMF may be stopped 7 days after initiation of systemic therapy.
Allogeneic hematopoietic stem cell infusion: Patients undergo infusion of bone marrow (preferred) or peripheral blood stem cells on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV beginning on day 8 and continuing until blood counts recover for 2 consecutive days.
Donor lymphocyte infusion (DLI): Patients with mixed chimerism (i.e., < 95% donor) and those with < 50% donor T-cell engraftment at any engraftment assessment time point are eligible for DLI, in the absence of GVHD. If mixed chimerism persists, escalating doses of CD3-positive lymphocytes are administered every 3-4 weeks, in the absence of GVHD.

After completion of study therapy, patients are followed from engraftment through day 100, and then at 6 months, 1 year, and annually thereafter for 2-5 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a positivity or Birbeck granules in lesions
Considered poor-risk, defined as multisystem disease with involvement of one or more risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)
- No isolated "lung only" LCH
Progressive disease after one of the following treatments:
- LCH-III protocol or other standard LCH-directed therapies
- At least 1 course of the current salvage protocol (i.e., LCH-2 2005) or similar therapy (e.g., cytosine arabinoside or cladrabine-based regimens)
HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB) available
- 1 locus mismatch for donor allowed
- Up to 2 loci mismatch for unrelated UCB allowed

PATIENT CHARACTERISTICS:

Any hematologic status (transfusion support allowed)
Adequate hepatic, renal, cardiac, and pulmonary function to undergo reduced-intensity hematopoietic cell transplantation (RI-HCT) including the following:
- Transaminases < 5 times upper limit of normal (ULN)
- Bilirubin < 3 times ULN (unless secondary to hepatic LCH)
- Creatinine ≤ 2 mg/dL (adults) (if creatinine > 1.2 OR history of renal dysfunction, must have estimated creatinine clearance > 40 mL/min)
- Creatinine clearance > 40 mL/min (pediatrics)
- Glomerular filtration rate ≥ 50mL/min
- No decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular ejection fraction ≥ 35%
- No pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active underlying LCH
- No isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying LCH
No uncontrolled active life-threatening infection
Not pregnant or nursing
Negative pregnancy test

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks after last attempted salvage chemotherapy treatment
No other concurrent chemotherapy agents (e.g., methotrexate) during entire transplantation period up to day 100 post-transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618540

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Study Chair:

K. Scott Baker, MD

Masonic Cancer Center, University of Minnesota

More Information

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

Responsible Party:	Masonic Cancer Center at University of Minnesota ( K. Scott Baker )
Study ID Numbers:	CDR0000587357, UMN-2007UC002, UMN-MT2006-07, UMN-0612M98407
Study First Received:	February 19, 2008
Last Updated:	October 25, 2008
ClinicalTrials.gov Identifier:	NCT00618540
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

Langerhans cell histiocytosis

Study placed in the following topic categories:

Melphalan
Lung Diseases, Interstitial
Langerhans cell histiocytosis
Fludarabine monophosphate
Histiocytosis, Langerhans-Cell
Histiocytosis X
Lymphatic Diseases

Letterer-Siwe disease
Histiocytosis
Respiratory Tract Diseases
Lung Diseases
Alemtuzumab
Fludarabine

Additional relevant MeSH terms:

Antimetabolites
Reticuloendotheliosis
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009