Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01490723
Recruitment Status : Active, not recruiting
First Posted : December 13, 2011
Last Update Posted : November 9, 2017
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Drug: Rituximab Drug: 111In Ibritumomab Procedure: Planar Scintigraphy Imaging Drug: 90Y IbritumomabTiuxetan Drug: Fludarabine Drug: Bendamustine Drug: Thymoglobulin Drug: Tacrolimus Drug: Methotrexate Drug: Mycophenolate Drug: G-CSF Procedure: Stem Cell Transplantation Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose-Intense Yttrium-90 Ibritumomab Tiuxetan (Zevalin)-Containing Non-Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in B-cell Malignancies
Actual Study Start Date : January 2013
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Arm Intervention/treatment
Experimental: Yttrium-90 Ibritumomab + Chemo
Day -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.
Drug: Rituximab
250 mg/m2 by vein preceding 111In Ibritumomab and (90Y) ibritumomab tiuxetan administration, respectively on Days -22 and -14.
Other Name: Rituxan

Drug: 111In Ibritumomab
(5.0 mCi +/- 10% of 111In) by vein immediately following the infusion of rituximab on Day -22.
Other Name: Zevalin

Procedure: Planar Scintigraphy Imaging
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.

Drug: 90Y IbritumomabTiuxetan
Calculated to deliver not below 10 Gy to normal organs (liver, lungs, kidneys) by vein post rituximab on Day -14.
Other Name: Zevalin

Drug: Fludarabine
30 mg/m2 intravenously on Days -5, -4, and -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Drug: Bendamustine
130 mg/m2 intravenously on D-5, -4 and -3.
Other Names:
  • Bendamustine Hydrochoride
  • Bendamustine HCL
  • CEP-18083
  • SDX-105
  • Treanda

Drug: Thymoglobulin
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).
Other Names:
  • ATG
  • Antithymocyte Globulin

Drug: Tacrolimus

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.

Other Name: Prograf

Drug: Methotrexate
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.

Drug: Mycophenolate
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).
Other Names:
  • MMF
  • Mycophenolate Mofetil
  • CellCept

Drug: G-CSF
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.
Other Names:
  • Filgrastim
  • Neupogen

Procedure: Stem Cell Transplantation
Stem Cell Transplantation on Day 0
Other Name: Allogeneic transplantation

Primary Outcome Measures :
  1. 100 Day Treatment-Related Mortality (TRM) [ Time Frame: 100 days ]
    The method of Thall, Simon, and Estey used to monitor the TRM rate within the first 100 days during the course of the trial. Computed Tomography (CT), Positron Emission Tomography (PET) scans, and bone marrow biopsy/aspirate to check the status of the disease.

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From date of treatment to date of relapse or death, up to 3 years ]
    Percentage of participants alive at 3 years, estimated using method of Kaplan and Meier. Overall survival calculated from date of transplant to date of relapse or death.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 18 to 70 years of age.
  2. 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.
  3. 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.
  4. 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.
  5. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
  6. Left ventricular EF >/= 45% with no uncontrolled arrythmias or symptomatic heart disease.
  7. FEV1, FVC >/= 60% and corrected DLCO >/= 60%.
  8. Serum creatinine </=1.6 mg/dL. Serum bilirubin < 2 mg/dL (unless due to Gilbert's Syndrome).
  9. SGPT < 2 X upper limit of normal.
  10. 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.
  11. 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.

Exclusion Criteria:

  1. Patient with active CNS involvement with lymphoid malignancy.
  2. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
  3. Patients with other malignancies diagnosed within 2 years prior to study registration. Skin squamous or basal cell carcinoma are exceptions.
  4. Active bacterial, viral or fungal infections.
  5. History of stroke within 6 months prior to study registration.
  6. A prior allogeneic stem cell transplant.
  7. Patient has received other investigational drugs within 3 weeks before study registration.
  8. Presence of circulating malignant lymphoid cells or bone marrow with lymphoma that constituted more than 25% of the cellular elements.
  9. Serious nonmalignant or malignant disease or psychiatric illness, which, in the opinion of the investigator would compromise protocol objectives or interfere with participation.
  10. Patients who are breast-feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01490723

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Spectrum Pharmaceuticals, Inc
Principal Investigator: Issa F. Khouri, MD,BS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01490723     History of Changes
Other Study ID Numbers: 2011-0393
NCI-2016-00250 ( Registry Identifier: NCI CTRP )
First Posted: December 13, 2011    Key Record Dates
Last Update Posted: November 9, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Chronic lymphocytic leukemia
CD20+ lymphoid malignancies
Diffuse large B-cell lymphoma
Allogeneic transplantation
In ibritumomab
Y ibritumomab
Fludarabine Phosphate
Bendamustine Hydrochloride
Bendamustine HCL
Stem Cell Transplantation
Planar Scintigraphy
Spect Scan
Single Photon Emission-Computed Tomography
CT Scan
Computed Tomography
Antithymocyte Globulin

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine phosphate
Mycophenolic Acid
Bendamustine Hydrochloride
Antibodies, Monoclonal
Antilymphocyte Serum
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action