Zevalin Before Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

NCT01811368 | Unknown Phase 2 DMC FDA Drug

• 3 other identifiers: 367905UCDCC#233NCI-2012-02753
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ibritumomab tiuxetan before donor peripheral blood stem cell transplant works in treating patients with relapsed or refractory non-Hodgkin lymphoma. Giving rituximab, antithymocyte globulin, and total-lymphoid irradiation (TLI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. Also, radiolabeled monoclonal antibodies, such as ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving rituximab, antithymocyte globulin, and TLI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Giving a radiolabeled monoclonal antibody before a donor peripheral blood stem cell transplant may be an effective treatment for non-Hodgkin lymphoma.

Conditions

Refractory Non Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Response conversion rate (PD/SD to PR and CR)

  Calculated along with 95% confidence intervals (CI). Logistic regression will be used to assess the impact of patient characteristics (e.g., low/high lactate dehydrogenase isoenzyme-3 \[LDH\] or immunologic correlates) on the response conversion rate.

  Up to 60 days post-transplant

Secondary Outcomes (6)

• Time to engraftment/chimerism

  Up to 3 years

• Rate of acute GVHD

  Up to day 730

• Rate of chronic GVHD

  Up to day 730

• Overall survival

  Up to day 730

• EFS

  2 years

Study Arms (1)

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive rituximab IV on days -21 and 14, ibritumomab tiuxetan IV on day -14, TLI on days -11 to -7 and -4 to -1, and antithymocyte globulin IV over 4-6 hours on days -11 to -7. Patients also undergo TLI on days -11 to -7 and -4 to -1. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO BID or IV on days -3 to 56 with taper to 6 months and mycophenolate mofetil PO BID or IV on days 0-28.

Biological: rituximab; Biological: ibritumomab tiuxetan; Biological: anti-thymocyte globulin; Radiation: total nodal irradiation; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil

Interventions

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, Mabthera, Rituxan

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

ibritumomab tiuxetan BIOLOGICAL

Given IV

Also known as: Zevalin

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

anti-thymocyte globulin BIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

total nodal irradiation RADIATION

Undergo TLI

Also known as: TLI, total lymphoid irradiation

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

peripheral blood stem cell transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplant

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

cyclosporine DRUG

Given PO or IV

Also known as: cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

mycophenolate mofetil DRUG

Given PO or IV

Also known as: Cellcept, MMF

Treatment (ibritumomab tiuxetan, allogeneic PBSCT)

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed relapsed cluster of differentiation (CD)20+ non-Hodgkin's lymphoma (NHL) (included in this category are follicular grade I, II, III, marginal zone, mantle cell, diffuse large B cell, small lymphocytic lymphoma) and CD20+ Hodgkin's disease for which standard curative therapy does not exist or is no longer effective
• Patients must have had at least one prior chemotherapeutic regimen; steroids alone and local radiation do not count as regimens; radiotherapy must have been completed at least 4 weeks prior to entry into the study; Rituxan alone does not count as a regimen; however, Bexxar or Zevalin (ibritumomab tiuxetan) do and patients must have completed radioimmunotherapy (RIT) \> 12 months prior to enrollment
• Karnofsky performance status of ≥ 60%
• Life expectancy of greater than 3 months
• Total bilirubin within institutional normal limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 times institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Blood counts no restrictions
• Patients who had anything less than a CR (PR, SD or progressive disease) to their last salvage regimen
• Ability to understand and the willingness to sign a written informed consent document
• Patients fit for non-myeloablative transplantation or best treatment that have an available matched (9/10 or better) related or unrelated donor
• Patients who are considered rituximab refractory (defined as progression within 6 months of their last rituximab-containing regimen)

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, rituximab within three months (unless there is evidence of progression), or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include the use of steroids which may continue until two days prior to enrollment
• Patients may not be receiving any other investigational agents
• Failure to obtain insurance/payment authorization for Zevalin, unless the subject agrees to cover the cost
• Patients with known active brain metastases, other neurological disorders/dysfunction or a history of seizure disorder, or other neurological dysfunction should be excluded from this clinical trial because of their poor prognosis
• Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month
• Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure; left ventricular ejection fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is \< 30%
• Patients requiring supplementary continuous oxygen; diffusion capacity of the lung of carbon monoxide (DLCO) is not required to be measured, however if it is measured, patient is excluded if DLCO \< 35%
• Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension
• Patients with any of the following liver function abnormalities will be excluded:
• Fulminant liver failure
• Cirrhosis with evidence of portal hypertension or bridging fibrosis
• Alcoholic hepatitis
• Esophageal varices
• A history of bleeding esophageal varices
• Hepatic encephalopathy

Sponsors & Collaborators

• Joseph Tuscano: lead
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (1)

University of California Davis

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; ibritumomab tiuxetan; Antilymphocyte Serum; thymoglobulin; Peripheral Blood Stem Cell Transplantation; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Joseph Tuscano

  UC Davis Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2013
• First Posted: March 14, 2013
• Study Start: March 12, 2013
• Primary Completion: April 1, 2023
• Study Completion: December 1, 2023
• Last Updated: November 30, 2022

Record last verified: 2022-11

Locations

US (1)