- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00771602
Alemtuzumab + Rituximab Consolidation in CLL
A Randomized Trial of Rituximab vs Alemtuzumab vs Alemtuzumab + Rituximab as Consolidation Therapy for Patients With Chronic Lymphocytic Leukemia (CLL) With Evidence of Residual Disease Following Prior Chemo(Immuno)Therapy
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Study Drugs:
Alemtuzumab and rituximab are both monoclonal antibodies. Monoclonal antibodies are proteins designed to attach to a protein on the surface of the leukemia cell. By attaching to the leukemia cell, monoclonal antibodies alert the immune system to target that cell and kill it.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of a dice) to 1 of 3 groups. Group 1 will receive rituximab alone. Group 2 will receive alemtuzumab alone. Group 3 will receive both drugs together.
At the beginning of the study, the chance of being assigned into any of the groups is about equal. However, once enough participants are on study and the response rate in each group is known, you will have a slightly better chance of being assigned to the group with the highest response rate.
Study Drug Administration:
Group 1:
If you are in Group 1, rituximab will be given through a needle in your vein 1 time a week for 4 weeks. The first time you receive rituximab, it will be given over about 4-6 hours. Depending on any side effects you may have, the later infusions may be given over about 2-4 hours.
Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine), Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try and prevent and/or help control side effects such as fevers and chills.
To help prevent infections, you will take the antibiotic valacyclovir (or a similar drug). Valacyclovir is taken 1 time a day every day. Your doctor will describe this to you in more detail.
Group 2:
If you are in Group 2, alemtuzumab will be given as an injection under your skin 3 times a week for 13 weeks. You will have to come to the clinic for each dose, learn how to inject it yourself, or have someone else taught how to inject you.
To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole (SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken 2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take the antibiotics for at least 3 months after your last dose of alemtuzumab.
Group 3:
If you are in Group 3, rituximab will be given through a needle in your vein 1 time a week for 4 weeks. The first time you receive the rituximab, it will be given over about 4-6 hours. Depending on any side effects you may have, the later infusions may be given over about 2-4 hours.
Alemtuzumab will be given as an injection under your skin 3 times a week for 13 weeks. You will have to come to the clinic for each dose, learn how to inject it yourself, or have someone else taught how to inject you.
Before each dose of rituximab, you will receive drugs such as benadryl (diphenhydramine), Tylenol (acetaminophen), and sometimes steroids (either by mouth or into your vein) to try and prevent and/or help control side effects.
To help prevent infections, you will take the antibiotic trimethoprin/sulfamethoxazole (SMX). Your doctor will tell you if you will take the tablet 2 times a day either 3 times a week (Monday, Wednesday, and Friday) or 2 times a week (Saturday and Sunday). You will also take either the antibiotic valganciclovir or valacyclovir. Valganciclovir tablets are taken 2 times every day. Valacyclovir is taken 1 time a day every day. You will continue to take the antibiotics for at least 3 months after your last dose of alemtuzumab.
Study Visits:
Every week while you are receiving therapy, blood (about 1 tablespoon) will be drawn for routine tests.
Six (6), 12, and 18 weeks (+/- 1 week) after you begin receiving the study drug(s) and then every 6 months (+/- 1 month) after that, you will have bone marrow biopsies and/or aspirates to check the status of the disease and to check for residual disease.
Every 6 months (+/- 3 months) after you have stopped receiving therapy, you will have a physical exam and blood (about 1 tablespoon) will be drawn for routine tests.
If you are in Group 2 or 3, during Week 3 and 6, blood (about 1 teaspoon) will be drawn to check for the cytomegalovirus (CMV) infection. This infection may occur in people with weakened immune systems.
If your doctor thinks it is necessary, you will have a chest x-ray and/or other scans.
Length of Study:
If you are in Group 1, you will take the study drug for up to 4 weeks. If you are in Groups 2 or 3, you will take the study drug(s) for up to 13 weeks. You will be taken off treatment early if you have intolerable side effects.
You will remain on study as long as the disease does not get worse.
This is an investigational study. Rituximab is FDA approved and commercially available for non-Hodgkin's lymphoma. However, it is not approved for the treatment of CLL.
Alemtuzumab is FDA approved and commercially available. It has been approved for the treatment of CLL when given by vein. It has not been approved to be given as an injection under the skin or for treatment after chemotherapy.
Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
-
-
Texas
-
Houston, Texas, Forenede Stater, 77030
- UT MD Anderson Cancer Center
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Patients with CLL, CLL/prolymphocytic leukemia (PLL), or Small Lymphocytic Lymphoma (SLL) who have achieved an National Cancer Institute-Working Group (NCI-WG) nodular partial (nPR) or complete response (CR) with documentation of residual disease by MRD flow cytometry following chemotherapy or chemoimmunotherapy.
- Patients with CLL, CLL/PLL, or SLL who have achieved an NCI-WG partial response (PR) following prior chemotherapy or chemoimmunotherapy.
- Age >/=18 years.
- ECOG performance status </=2.
- Serum creatinine </= 2 mg/dL; serum total bilirubin </= 2 mg/dL; serum AST or ALT <4 x ULN.
- Signed informed consent.
- Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients of childbearing potential (non-childbearing is defined as >/= 1 year post-menopausal or surgically sterilized) need a negative serum or urine pregnancy test within 14 days of study enrollment.
Exclusion Criteria:
- Past history of anaphylaxis following exposure to rat or mouse derived complementarity determining region (CDR)-grafted humanized monoclonal antibodies.
- Hormonal therapy within 2 weeks prior to study start. Hormonal replacement therapy is permitted.
- Active Hepatitis B (at least one of the following markers positive: HBsAg, HBeAg, IgM anti-HBc, HBV DNA).
- Previous treatment with alemtuzumab plus rituximab in combination.
- Pregnant or nursing women.
- History of HIV infection.
- Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Less than 6 months from the completion of prior chemotherapy or chemoimmunotherapy. Completion of prior chemoimmunotherapy is defined as the last day of therapy of the respective treatment regimen.
- Symptomatic CNS disease.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Rituximab
Group 1: 375 mg/m^2 IV Rituximab Alone
|
375 mg/m^2 by standard IV (intravenous) infusion on days 1, 8, 15, and 22 of weeks 1-4.
Andre navne:
|
|
Eksperimentel: Alemtuzumab
Group 2: 30 mg SQ Alemtuzumab Alone
|
Dose escalation of 3, 10 and 30 mg subcutaneously (SQ) during week 1, followed by dose of 30 mg subcutaneously three times weekly (e.g.
Monday-Wednesday - Friday) starting on week 2 for a total of 12 weeks (2-13).
Andre navne:
|
|
Eksperimentel: Rituximab + Alemtuzumab
Group 3: 375 mg/m^2 Rituximab + 30 mg SQ Alemtuzumab
|
375 mg/m^2 by standard IV (intravenous) infusion on days 1, 8, 15, and 22 of weeks 1-4.
Andre navne:
Dose escalation of 3, 10 and 30 mg subcutaneously (SQ) during week 1, followed by dose of 30 mg subcutaneously three times weekly (e.g.
Monday-Wednesday - Friday) starting on week 2 for a total of 12 weeks (2-13).
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of Patients With Molecular Remissions at 52 Weeks
Tidsramme: 52 weeks
|
Molecular Remissions (minimal residual disease (MRD) flow cytometry-negative) after monoclonal antibody consolidation therapy.
Molecular remission is defined as resolution of all detectable disease below the limits of the MRD flow cytometry assay sensitivity.
|
52 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression-free Survival
Tidsramme: 52 weeks or until disease progression
|
Progression-free survival (PFS) is measured from date of trial entry until documented progression of disease or death from any cause.
|
52 weeks or until disease progression
|
|
52 Week Toxicity Rate
Tidsramme: 52 weeks
|
The definition of toxicities include any >/= grade 3 non-hematologic toxicity, >/= grade 3 infection, and any symptomatic (i.e.
febrile) documented CMV (cytomegalovirus) reactivation, according to NCI-WG definitions.
|
52 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Stefan Faderl, M.D., M.D. Anderson Cancer Center
Publikationer og nyttige links
Hjælpsomme links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Leukæmi, B-celle
- Leukæmi
- Leukæmi, lymfatisk, kronisk, B-celle
- Leukæmi, lymfoid
- Lægemidlers fysiologiske virkninger
- Antirheumatiske midler
- Antineoplastiske midler
- Immunologiske faktorer
- Antineoplastiske midler, immunologiske
- Rituximab
- Alemtuzumab
Andre undersøgelses-id-numre
- 2006-0767
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