Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)
Dose-Intense Yttrium-90 Ibritumomab Tiuxetan (Zevalin)-Containing Non-Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in B-cell Malignancies
2 other identifiers
interventional
20
1 country
1
Brief Summary
The goal of this clinical research study is to learn if adding Zevalin (ibritumomab tiuxetan) to low-intensity chemotherapy (the combination of rituximab, bendamustine, and fludarabine), followed by an allogeneic stem cell transplant, can help to control lymphoma. The safety of this combination will also be studied. Two (2) forms of ibritumomab tiuxetan will be used in this study. 90Y-ibritumomab tiuxetan is designed to attach to lymphoma cells and destroy the cells using a radioactive particle that is attached to it. 111In-ibritumomab tiuxetan is like 90Y- ibritumomab tiuxetan, but the radioactive particle that is attached to it does not kill lymphoma cells. The radioactive particle makes the drug able to be seen inside your body. It is being used in this study to predict how fast the study drug will travel in the body and how long the drug stays in the body. Rituximab is designed to attach to lymphoma cells, which may cause them to die. Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells. Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 leukemia
Started Jan 2013
Typical duration for phase_2 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 9, 2011
CompletedFirst Posted
Study publicly available on registry
December 13, 2011
CompletedStudy Start
First participant enrolled
January 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
April 24, 2019
CompletedResults Posted
Study results publicly available
May 5, 2020
CompletedMay 5, 2020
April 1, 2020
6.3 years
December 9, 2011
April 13, 2020
April 23, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Treatment-Related Mortality (TRM)
Number of participants without treatment related mortality at day 100.
100 days
Secondary Outcomes (1)
Overall Survival (OS)
From date of treatment to date of relapse or death, up to 3 years
Study Arms (1)
Yttrium-90 Ibritumomab + Chemo
EXPERIMENTALDay -22 and -14, Rituximab 250 mg/m2 preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively. Day -22, -21 to -16, Imaging, repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Day -14, (90Y) ibritumomab tiuxetan administration. Day -5, -4 and -3, Fludarabine and Bendamustine following Stem Cell Transplant (SCT) and CT. Fludarabine 30 mg/m2 intravenously followed by Bendamustine 130 mg/m2 intravenously. All patients receive Graft Versus Host Disease (GvHD) prophylaxis, infections disease prophylaxis, growth factors, blood and platelet transfusion and other supportive treatment.
Interventions
250 mg/m2 by vein preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively on Days -22 and -14.
(5.0 mCi +/- 10% of 111In) by vein immediately following the infusion of rituximab on Day -22.
Day -22, -21 to -16: Planar scintigraphy whole-body imaging started on Day -22 post 111In Ibritumomab infusion prior to voiding, and repeated 3-6 hours later (including Single Photon Emission-Computed Tomography/Computed Tomography (SPECT/CT) scan of the abdomen). Whole-body planar scintigraphy imaging will be repeated between 22-26 hours, then between 70-74 hours, and later between 142-146 hours post 111In Ibritumomab injection.
Calculated to deliver not below 10 Gy to normal organs (liver, lungs, kidneys) by vein post rituximab on Day -14.
30 mg/m2 intravenously on Days -5, -4, and -3.
130 mg/m2 intravenously on D-5, -4 and -3.
1 mg/kg (based on actual body weight) on Days -2 and -1 will be administrated to patients receiving a cord blood (CB) and a matched unrelated donor (MUD).
Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no Graft versus Host Disease (GVHD) is present. For patients receiving cord blood (CB) graft, the Graft versus Host Disease (GvHD) prophylaxis will be with Tacrolimus. Tacrolimus will start on D-2 administrated at starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on D -2 and will be tapered around Day +180 if no GvHD is present.
5 mg/m2 by vein on Day +1, +3 and +6. Patients receiving an unrelated graft will also be given methotrexate on Day +11 after the transplant.
15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth administered from Days -3 to +45 and then tapered to end by day 100 if there is no Graft versus Host Disease (GVHD).
5 mcg/kg/day subcutaneously beginning Day +7 for patients receiving related and matched unrelated donor (MUD) grafts and on Day 0 for patients receiving a cord blood (CB). G-CSF will continue until the absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.
Stem Cell Transplantation on Day 0
Eligibility Criteria
You may qualify if:
- to 70 years of age.
- Patients with the following CD20+ lymphoid malignancies who are eligible for allogeneic transplantation: a. Relapsed or refractory follicular lymphoma; b. Relapsed or refractory or high risk mantle cell lymphoma (hi ki67; blastic); c. Recurrent or refractory marginal zone; d. Recurrent or refractory CLL/small lymphocytic lymphoma; e. Double-hit lymphoma; f. Diffuse large B cell lymphoma; g. Richter's patients; or h. Refractory or recurrent Burkitts.
- Patients who meet criterion #2 or have any of the following are eligible: a. Less than PR to salvage chemotherapy; b. Kinetic failure; c. Having received more than 3 lines of therapy; d. Failure to mobilize autologous stem cell; e. 10% or more marrow involvement; f. 6 months post autologous stem cell transplant.
- Patients must have a fully-matched related donor or a matched unrelated donor identified. Double cord (at least 4/6 matched) can be used if no adult matched donor is available.
- Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
- Left ventricular EF \>/= 45% with no uncontrolled arrythmias or symptomatic heart disease.
- FEV1, FVC \>/= 60% and corrected DLCO \>/= 60%.
- Serum creatinine \</=1.6 mg/dL. Serum bilirubin \< 2 mg/dL (unless due to Gilbert's Syndrome).
- SGPT \< 2 X upper limit of normal.
- Men and women of reproductive potential must agree to follow accepted birth control methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Negative Beta HCG test within 30 days in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization). Pregnancy testing is not required for post-menopausal or surgically sterilized women.
You may not qualify if:
- Patient with active CNS involvement with lymphoid malignancy.
- Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
- Patients with other malignancies diagnosed within 2 years prior to study registration. Skin squamous or basal cell carcinoma are exceptions.
- Active bacterial, viral or fungal infections.
- History of stroke within 6 months prior to study registration.
- A prior allogeneic stem cell transplant.
- Patient has received other investigational drugs within 3 weeks before study registration.
- Presence of circulating malignant lymphoid cells or bone marrow with lymphoma that constituted more than 25% of the cellular elements.
- Serious nonmalignant or malignant disease or psychiatric illness, which, in the opinion of the investigator would compromise protocol objectives or interfere with participation.
- Patients who are breast-feeding.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Spectrum Pharmaceuticals, Inccollaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Issa F. Khouri, M.D., Stem Cell Transplantation
- Organization
- U.T. MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Issa F. Khouri, MD,BS
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 9, 2011
First Posted
December 13, 2011
Study Start
January 1, 2013
Primary Completion
April 24, 2019
Study Completion
April 24, 2019
Last Updated
May 5, 2020
Results First Posted
May 5, 2020
Record last verified: 2020-04