Cold Agglutinin Disease

Autoimmune Hemolytic Anemia

Bendamustine, Rituximab

Herlev University Hospital

Turku University Hospital

Haukeland University Hospital

Vestre Viken Hospital

Haugesund Hospital

Akershus University Hospital

Oslo University Hospital

St Olav University Hospital

Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease

The CAD5 Study::Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicenter Trial on the Safety and Efficacy of Bendamustine and Rituximab Combination Therapy

Responses will be assessed using the following, previously published definitions:
Complete response (CR), Absence of anemia, no signs of hemolysis, no clinical symptoms of CAD, undetectable serum monoclonal protein, and no signs of clonal lymphoproliferation by bone marrow histology, immunohistochemistry and flow cytometry.
Partial response (PR), Stable increase in hemoglobin levels by at least 2.0 g/dL or to the normal range, combined with a reduction of serum IgM concentrations by at least 50% or to the normal range, improvement of clinical symptoms, and transfusion independency.
Non-response (NR), Patients not meeting the criteria for CR or PR.

Time to response (TTR) is the time from start of therapy to the achievement of any degree of response.

Time to best response (TTBR) is the time from start of therapy to the observation of the highest hemoglobin level achieved + 0.5 g/dL.

Response duration is the time from achievement of any degree of response to relapse. Relapse is defined by one or more of the following events: A decline in hemoglobin level by at least 2.0 g/dL from the highest level achieved or to below 10.0 g/dL; transfusion requirement; or recurrence of significant cold-induced circulatory symptoms.

Data are to be shared between authors before final analysis and publication.

Sigbjorn Berentsen

MD, PhD

Helse Fonna

Standard anti-emetic prophylaxis consisting of 1/dexamethasone 6 mg daily during the chemotherapy days and 2/tropisetron (Navoban)5 mg daily during chemotherapy and 2 days after

Aprepitant given orally 125 mg the first day, then 80 mg daily during the chemotherapy course and 7 days after as an addition to standard antiemetic therapy as in the placebo arm.

Nausea

Vomiting

Aprepitant will be added to the standard anti-emetic therapy. Emend is given orally, 125 mg the first day, then 80 mg daily during the chemotherapy course and 7 days after

Aprepitant (Emend)

Placebo will be administered instead of Emend

Placebo

Uppsala University Hospital

Treatment of Chemotherapy-induced Nausea and Vomiting

A Randomized Controlled Study to Compare (EMEND®)to Standard Treatment as Prevention for Delayed Chemotherapy-induced Nausea and Vomiting (CINV) After Myeloablative Therapy for Patients Undergoing Autologous Stem Cell Transplantation.

The proportion of patients with a complete response (no vomiting and/or only mild nausea and no use of rescue therapy) a/ during chemotherapy and b/ in the delayed phase (up to 7 days after end of chemotherapy).

Possible side effects will be recorded, and all AE:s reported during 3 weeks after the chemotherapy.

Gunnar Birgegard

Prof

Patients will receive one (1) four (4) week cycle of weekly IV PS-341 followed by a standard of care radical prostatectomy 24 to 72 hours later.

PS-341

Age of participants is reported as age at the time of study enrollment.

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Region of Enrollment

Pour wound healing is defined in the protocol as dehiscence of fascia during the first postoperative week. Excessive bleeding is defined in the protocol as greater than 2 units of blood required during the first 24 hours after surgery.

The Purpose of the Present Study is to Assess the Safety of PS-341 as a Pretreatment in Patients Who Are to Undergo a Radical Prostatectomy. Poor Wound Healing and Excessive Bleeding, With Historical Rates of <1% and 10% Respectively Will be Measured.

Overall Study

Dr. Teresa Hayes - Associate Professor

Prostate Neoplasms

PS-341 is a dipeptidyl boronic acid inhibitor with high specificity for the proteasome developed by Millennium Pharmaceuticals Inc. to treat human malignancies. It is the first member of this class of anti-tumor agents to come to human trials. Patients will receive PS-341 (1.6mg/m2/dose) by intravenous push weekly for 4 consecutive weeks followed by a 24-72 hour rest. This schedule consists of one treatment cycle. Upon the completion of 4 weeks of PS-341 followed by a 24-72 hour rest period, radical prostatectomy will be performed.

PS-341 (bortezomib)

Scott Department of Urology Clinical Trials

Scott Department of Urology, Baylor College of Medicine

PS-341 Followed by Removal of Prostate for Those With Prostate Cancer

H-11047: A Study of PS-341 Followed by Radical Prostatectomy for Patients With Adenocarcinoma of the Prostate (Spore #: 11-01-30-13)

Teresa Hayes

Associate Professor

Baylor College of Medicine

Millennium Pharmaceuticals, Inc.

Patients not responding to high- dose zidovudine and valganciclovir alone may be treated with botezomib plus high- dose zidovudine and valganciclovir

Single agent sirolimus for patients where targeted oncolytic virotherapy seems suboptimal

EPOCH chemotherapy with rituximab may be utilized to rescue such patients, with the intent of stabilizing suchpatients

Rituximab with liposomal doxorubicin (R-Dox) followed by consolidation or lmaintenancel therapy with dose escalating interferon-alpha

Lymphoproliferative Disorder

HHV-8

Malignancy

Etoposide 50 mg/m2 /day continuous intravenous infusion (CIVI) over 24 hours x 4 days (days 1-4) of 21 day cycle. A maximum of 6 cycles of R-EPOCH-R will be administered except in exceptional circumstances.

Etoposide

Ages 18 and over: Initial dose of 7.5 million units subcutaneous, three times weekly x 14 days; subsequent dosesincrease dose as tolerated each 14 days to a maximum of 45 million units subcutaneous three times weekly; Ages 12-17: Initial dose of 5 million units/m2 subcutaneous, three times weekly x 14 days Subsequent doses: Increase dose as tolerated each 14 days to a maximum of 30 million units/m2 subcutaneous, three times weekly

Interferon-alpha

Rituximab 375 mg/m2 IV day 1, shall be administered prior to Doxil injection. When combined with EPOCH chemotherapy, Rituximab will be given on days 1 and 5.

Rituximab

Cycle 1: Zidovudine 600 mg PO QID x 7-21 days in outpatient setting;600 mg PO q6hours x 7-21 (Intravenous zidovudine 300 mg q 6 hours may be substituted) days for inpatients; Cycle 2 and beyond: 600 mg PO QID x 7 days in outpatient setting; 600 mg PO q 6 hours x 7 days (300 mg q 6 hours may be substituted)

Zidovudine

21 day cycle; 20 mg/m2 Liposomal Doxorubicin given on day 1 and shall be administered after completion of Rituximab infusion from 2 to 6 cycles.

Liposomal Doxorubicin

1.3 mg/m2 IV days 1, 4, 8, and 11. Cycle length is 21 days.

Bortezomib

Cycle 1: Valganciclovir 900 mg PO BID x 7-21 days in outpatient setting; 900 mg PO q 12 hours x 7-21 days for inpatients; Cycle 2 and beyond: 900 mg PO BID x 7 days for outpatients; 900 mg PO q 12 hours x 7 days (Intravenous ganciclovir 5 mg/kg may be substituted) for inpatients

Valganciclovir

10 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

Doxorubicin

0.4 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.

Vincristine

Cyclophosphamide: if CD4 < 100 cells/mm3, 187 mg/m2 IV (Day 5) if CD4 greater than or equal to 100 cells/mm3, 375 mg/m2 IV (Day 5) of 21 day cycle.

Cyclophosphamide

Filgrastim 300 micrograms subcutaneous daily beginning day 6 until absolute neutrophil count recovery 5000 cells/mm3 (Pegfilgrastim may be substituted with PI approval, at the recommended dose of one 6mg syringe)

Filgrastim (G-CSF)

Prednisone 60 mg/m2/day PO x 5 days (days 1-5)of 21 day cycle.

Prednisone

Maximum daily dose of 40 mg given as a single agent on 21 day cycle.

Sirolimus

Observation Only

National Institutes of Health Clinical Center, 9000 Rockville Pike

Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity

Preliminarily assess the feasibility of risk-stratifying patients according to disease parameters associated with MCD

To study in a preliminary fashion the therapeutic efficacy and toxicity of several rationally designed therapeutic approaches to KSHV-MCD aimed at KSHV cytoreductive therapy, or therapy aimed at suppressing KSHV-induced pathogenic mechanisms:-High-dose zidovudine combined with valganciclovir (HDAZT+VGCV)-Bortezomib in combination with (HDAZT+VGCV)-Sirolimus-Rituximab in combination with liposomal doxorubicin followed by Interferon- or high-dose AZT with valganciclovir-EPOCH-R (rituximab combined with oral prednisone and infusional etoposide, vincristine, and doxorubicin followed by bolus cyclophosphamide, prednisone and rituximab)

Preliminarily assess additional rationally designed treatments for MCD aimed at KSHV reductive therapy

percentage of patients alive until study closure

the length of time during and after the treatment that patients live with the disease but it does not get worse

lymphoproliferative disorders/nausea

Bendamustine and Rituximab Combination Therapy for Cold Agglutinin Disease

Treatment of Chemotherapy-induced Nausea and Vomiting

PS-341 Followed by Removal of Prostate for Those With Prostate Cancer

Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

科学支持的最完整的草药数据库