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Chimeric Monoclonal CD-20 Antibody (Rituximab) for Steroid Refractory Acute Graft Versus Host Disease (SR-aGVHD): A Pilot Study


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Trial Information

Chimeric Monoclonal CD-20 Antibody (Rituximab) for Steroid Refractory Acute Graft Versus Host Disease (SR-aGVHD): A Pilot Study


OBJECTIVES:

- To determine the overall survival of patients with steroid-refractory acute
graft-versus-host disease at 180 days after treatment with rituximab.

- To evaluate the safety of this drug in these patients.

- To evaluate the clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on days 1, 7, 14, and 21 in the absence of disease progression
or unacceptable toxicity. Two weeks after completion of study therapy, patients achieving a
partial response receive 4 more weekly doses of rituximab.

Patients continue corticosteroid therapy (i.e., methylprednisone IV at the study entry dose
or an equivalent oral dose of prednisone) and immunosuppression (i.e., cyclosporine or
tacrolimus) as prescribed for graft-versus-host disease (GVHD) prophylaxis until at least 1
week after completion of rituximab. In the event of acute GVHD improvement, corticosteroid
therapy is tapered.

After completion of study therapy, patients are followed for up to 1 year.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of acute graft-versus-host disease (aGVHD) meeting the following criteria:

- Steroid-refractory and meeting any of the following organ-staging criteria:

- No change in the stage of skin aGVHD after treatment with
methylprednisolone at a dose of 2 mg/kg per day or more for 1 week

- Progression of aGVHD of skin by at least 1 stage OR no response of visceral
(liver, GI) aGVHD despite treatment with methylprednisolone at a dose of 2
mg/kg per day or more for at least 72 hours

- Progression of visceral aGVHD despite treatment with methylprednisolone at
a dose of 2 mg/kg per day or more for at least 48 hours

- Progression of visceral aGVHD to stage 4 after treatment with
methylprednisolone at a dose of 2 mg/kg per day or more for 24 hours

- Grade II-IV aGVHD requiring systemic therapy within 24-48 hours of diagnosis

- Biopsy confirmation of aGVHD is strongly recommended but not required

- No isolated upper gastrointestinal GVHD as sole manifestation of aGVHD

- No isolated grade I or II skin GVHD as sole manifestation of aGVHD

- Patients must have received prior corticosteroids at a dose of 2 mg/kg/day or
more for at least 72 hours as first-line aGVHD treatment

- Have undergone hematopoietic stem cell transplantation for any indication and from
any allogeneic graft and donor type (i.e., marrow or peripheral blood,
matched-related or matched-unrelated) within the past 100 days

- Absolute neutrophil count > 500/mm^3 times 3 days (must have evidence of
engraftment)

- No prior autologous or syngeneic transplantation

- No chronic GVHD, defined as GVHD occurring beyond 100 days of the hematopoietic
transplant

- No development of GVHD after prior donor lymphocyte infusion

- No post-transplantation lymphoproliferative disorder

- Patients failing to respond to second-line aGVHD treatment with infliximab or other
second-line therapy are allowed

- Rituximab is administered as 3rd-line aGVHD therapy

PATIENT CHARACTERISTICS:

- See Disease Characteristics

- Karnofsky performance status 30-100%

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy

- No uncontrolled infection (i.e., documented bacterial, viral, or fungal infection
within 72 hours prior to study entry)

- Concurrent prophylactic, empiric, or therapeutic use of antibiotics (i.e., taken
concurrently for a controlled infection) allowed

- Clostridium difficile infection allowed

- More than 8 weeks since documentation of any of the following opportunistic
infections:

- Pneumocystis carinii

- Aspergillosis

- Histoplasmosis

- Atypical mycobacterium infection

- Other pathogenic molds or fungi

- No hypotension believed to be secondary to sepsis syndrome or heart failure requiring
> 1 inotropic agent, or dopamine > 5 mcg/kg/min for blood pressure support

- No mechanical ventilatory support

- No relapsed, refractory, or second malignancies at the time of study entry

- No prior grade IV severe adverse reaction to rituximab

- No allergy to murine products

- No documented HIV infection

- No grade IV renal, hepatic, pulmonary, or neurologic toxicity

- No congestive heart failure, defined as cardiac dysfunction requiring inotropic
support other than dopamine at ≤ 5 mcg/kg/min

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior rituximab in the conditioning regimen for hematopoietic stem cell
transplantation

- No prior prophylactic immunosuppression tapered or stopped for treatment of leukemia
relapse or minimal residual disease

- More than 2 weeks since other prior investigational agents for GVHD treatment or
prophylaxis

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Survival at day 180 after treatment with rituximab

Safety Issue:

No

Principal Investigator

Rammurti Kamble, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Baylor College of Medicine

Authority:

United States: Federal Government

Study ID:

CDR0000582348

NCT ID:

NCT00624897

Start Date:

June 2007

Completion Date:

Related Keywords:

  • Cancer
  • graft versus host disease
  • stage III adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone 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
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • 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, BCR-ABL1 negative
  • blastic phase chronic myelogenous leukemia
  • childhood acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • juvenile myelomonocytic leukemia
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • refractory chronic lymphocytic leukemia
  • refractory hairy cell leukemia
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • childhood myelodysplastic syndromes
  • chronic eosinophilic leukemia
  • primary myelofibrosis
  • chronic neutrophilic leukemia
  • de novo myelodysplastic syndromes
  • disseminated neuroblastoma
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • high risk metastatic gestational trophoblastic tumor
  • previously treated childhood rhabdomyosarcoma
  • previously treated myelodysplastic syndromes
  • recurrent Wilms tumor and other childhood kidney tumors
  • recurrent childhood rhabdomyosarcoma
  • recurrent neuroblastoma
  • recurrent ovarian epithelial cancer
  • recurrent ovarian germ cell tumor
  • recurrent malignant testicular germ cell tumor
  • secondary myelodysplastic syndromes
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage II ovarian epithelial cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • stage III malignant testicular germ cell tumor
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • refractory multiple myeloma
  • Graft vs Host Disease
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Methodist HospitalHouston, Texas  77030
Texas Children's Cancer Center and Hematology Service at Texas Children's HospitalHouston, Texas  77030-2399