Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant - 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:	NCT00617929

Purpose

RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with clofarabine and rituximab works in treating patients after an unsuccessful stem cell transplant.

Condition	Intervention	Phase
Cancer	Biological: anti-thymocyte globulin Biological: filgrastim Biological: rituximab Drug: clofarabine Drug: cyclosporine Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Bone Marrow Transplantation Breast Cancer Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma

Drug Information available for: Cyclosporine Cyclosporin Mycophenolate mofetil hydrochloride Filgrastim Clofarabine Mycophenolate Mofetil Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	Conditioning for Graft Failure After Hematopoietic Stem Cell Transplantation

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

Primary Outcome Measures:

Sustained donor engraftment at 42 days post transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Treatment-related mortality at day 100 [ Designated as safety issue: Yes ]
Time to primary neutrophil engraftment at day 42 post transplantation [ Designated as safety issue: No ]
Survival at day 100 and 1 year [ Designated as safety issue: No ]
Chimerism [ Designated as safety issue: No ]
Acute graft-vs-host disease [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	January 2008
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the rate of sustained donor engraftment at 42 days and survival at 100 days post transplantation in patients treated with anti-thymocyte globulin, clofarabine, and rituximab.

Secondary

To determine incidence of treatment-related mortality at day 100 post transplantation.
To determine incidence of neutrophil recovery by day 42 post transplantation.
To determine survival at day 100 and 1 year post transplantation.
To determine the proportion of patients with chimerism at day 28 post transplantation.
To determine incidence and severity of grades II-IV acute graft-vs-host disease by day 100 post transplantation.

OUTLINE:

Conditioning regimen: Patients receive rituximab IV on day -7, anti-thymocyte globulin IV over 4-6 hours on days -6 to -4, and clofarabine IV over 1 hour on days -4 to -2.
Hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients may receive umbilical cord blood, peripheral blood stem cells, or bone marrow from unrelated or related donors.
Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral cyclosporine twice daily or cyclosporine IV every 8 hours beginning on day -3 and continuing for 100 or 180 days post transplantation followed by a taper; mycophenolate mofetil IV every 8 hours beginning on day -3 and continuing for 30 days (or 7 days after engraftment with no evidence of GVHD); and filgrastim (G-CSF) IV once daily beginning on day 1 and continuing until blood counts recover. After completion of study therapy, patients are followed on days 100, 180, and 360.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Inclusion criteria:

Must be in primary or secondary graft failure after hematopoietic stem cell transplantation, defined as a > 50% loss of donor chimerism* from previous maximum or less than 25% donor beyond day +42 with pancytopenia and no evidence of relapse
- Primary graft failure is defined as bone marrow at < 10% cellularity and ANC < 500/mm³ on 2 occasions after day 28 post transplantation
- Secondary graft failure is defined as < 5% cellularity and ANC < 500/mm³ for more than 7 days any time after primary engraftment NOTE: *Donor chimerism need not be considered if there is no evidence of malignancy
Patients with any diagnosis, type of donor, hematopoietic cell graft, or prior conditioning regimen allowed
- Related donors must be 2 to 75 years of age and in good health

Exclusion criteria:

Evidence of recurrence of primary malignancy
Autologous recovery defined as greater than 90% recipient PCR product in the competitive VNTR PCR performed on gradually increasing white blood cell count

PATIENT CHARACTERISTICS:

Inclusion criteria:

See Disease Characteristics
ANC < 500/mm³
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

Exclusion criteria:

Uncontrolled active infection, defined as more than one week with no response to appropriately chosen antibiotics
Allergy to rituximab
Evidence of HIV infection or positive HIV serology

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617929

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

Principal Investigator:

Jakub Tolar, MD

Masonic Cancer Center, University of Minnesota

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:	Masonic Cancer Center at University of Minnesota ( Jakub Tolar )
Study ID Numbers:	CDR0000587062, UMN-2007LS072, UMN-MT2007-07
Study First Received:	February 15, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00617929 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis

chronic myelomonocytic leukemia
chronic neutrophilic leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
disseminated neuroblastoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma

Study placed in the following topic categories:

Chronic Myelomonocytic Leukemia
Blast Crisis
Cyclosporine
Miconazole
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Cyclosporins
Follicular Lymphoma
Mycoses
Acute Myelocytic Leukemia
Preleukemia
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Wilms' Tumor
Mycophenolate mofetil

Neoplasm Metastasis
Lymphoma, Large-Cell, Anaplastic
Hodgkin Disease
Rhabdomyosarcoma
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Testicular Cancer
Rituximab
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Hairy Cell Leukemia
Myeloproliferative Disorders
Juvenile Myelomonocytic Leukemia
Breast Neoplasms

Additional relevant MeSH terms:

Anti-Infective Agents
Cyclosporine
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclosporins
Antifungal Agents
Therapeutic Uses
Lymphoma, Large-Cell, Immunoblastic
Mycophenolate mofetil
Lymphoma
Dermatologic Agents
Clofarabine

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Lymphatic Diseases
Neoplasms
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on May 07, 2009