Y Zevalin and BEAM in Autologous Stem Cell Transplantation (ASCT) for Lymphoma

NCT01538472 | Completed Phase 1 Results

• 1 other identifier: ID03-0123
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to see if high-dose chemotherapy (BEAM) and rituximab, given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells is safe. Another goal is to learn if this treatment can help decrease the chances of the cancer coming back.

Conditions

Lymphoma

Keywords

Lymphoma; Relapse B-cell CD20+ non-Hodgkin's lymphoma; High-dose BEAM chemotherapy; Y Zevalin; In Zevalin; Rituxan; Rituximab; BCNU; 1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea; Carmustine; BiCNU; VP-16; Ara-C; Cytarabine; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Melphalan; Alkeran; G-CSF; Filgrastim; Neupogen; Stem cell infusion; Autologous stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• Overall Survival Median

  Overall survival reported as number of days participants alive following treatment up to 5 years with annual follow up till disease progression. Evaluations done every 3 months for 1 year and then every 6 months for 5 years to check on the status of the disease, with long-term follow up as needed.

  Participant followed from baseline treatment to 5 years, with study total period 8 years (study duration)

• 3-Year Overall Survival

  Number of participants alive 3 years following treatment. Evaluations done every 3 months for 1 year and then every 6 months to check on the status of the disease.

  3 years

Study Arms (1)

Y Zevalin + BEAM

EXPERIMENTAL

Rituxan 250 mg/m2 preceding imaging dose of 111In Zevalin (5 mCi); additional infusion 250 mg/m2 Rituxan followed by therapeutic dose of 0.4 mCi/kg 90Y Zevalin received one week after Rituxan/111In Zevalin infusions. One week later, chemotherapy received with BCNU (300 mg/m2, intravenously (IV) day -6) VP-16 (200 mg/m2 IV every 12 hours, days -5 to -2) cytarabine (200 mg/m2 IV every 12 hours, days -5 to -2) and melphalan (140 mg/m2 IV day -1). Autologous stem cell infused on day 0 then Rituximab 1000 mg/m2 on days +1, and +8 post transplantation. G-CSF 5 mg/kg given daily starting Day 0 till recovery of granulocytes of 4.0 \* 109/L.

Drug: Y Zevalin; Drug: In Zevalin; Drug: Rituxan; Drug: BCNU; Drug: VP -16; Drug: Ara-C; Drug: Melphalan; Procedure: Stem Cell Infusion; Drug: G-CSF

Interventions

Y Zevalin DRUG

Starting dose: 0.4 mCi/kg by vein after Rituxan infusion on Day -14.

Y Zevalin + BEAM

In Zevalin DRUG

Imaging dose: 5 mCi by vein following Rituxan infusion on Day -21.

Y Zevalin + BEAM

Rituxan DRUG

250 mg/m2 by vein on Day -21 and on Day -14. 1000 mg/m2 by vein on Days +1 and +8.

Also known as: Rituximab

Y Zevalin + BEAM

BCNU DRUG

300 mg/m2 by vein on Day -6.

Also known as: Carmustine, BiCNU, 1,3-bis(2-chloroethyl)-1-nitrosourea bis-chloronitrosourea

Y Zevalin + BEAM

VP -16 DRUG

200 mg/m2 by vein every 12 hours on Days -5, -4, -3, and -2.

Y Zevalin + BEAM

Ara-C DRUG

200 mg/m2 by vein every 12 hours on Days -5, -4, -3,and -2.

Also known as: Cytarabine, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Y Zevalin + BEAM

Melphalan DRUG

140 mg/m2 by vein on Day -1.

Also known as: Alkeran

Y Zevalin + BEAM

Stem Cell Infusion PROCEDURE

Autologous stem cell infusion on Day 0.

Y Zevalin + BEAM

G-CSF DRUG

5 mg/kg by vein daily starting Day 0 till recovery of granulocytes of 4.0 x 109/L.

Also known as: Filgrastim, Neupogen

Y Zevalin + BEAM

Eligibility Criteria

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

You may qualify if:

• Relapsed CD20-positive B-cell non-Hodgkin's lymphoma (NHL) (demonstrated in lymph nodes or bone marrow), chemosensitive (at least Partial Remission (PR)).
• No anti-cancer therapy started within three weeks, prior to study initiation, and fully recovered from all toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy. No prior Rituximab within three weeks of starting therapy.
• No prior radioimmunoconjugate therapy.
• If patients had prior radiation, this should have not involved more than 25% of the bone marrow.
• An IRB-approved signed informed consent.
• Age: 18 to 65 years of age.
• Acceptable hematologic status within two weeks prior to patient registration, including: Absolute neutrophil count (\[segmented neutrophils + bands\] \* total white blood count (WBC)) \> 1,500/mm3. Platelet counts \> 100,000/mm3.
• Patients determined to have \<10% bone marrow involvement with lymphoma within four weeks before stem cell collection as defined by bilateral aspirates and biopsies.
• Prestudy performance status of 0, 1, or 2 according to the World Health Organization (WHO).
• Female patients included must not be pregnant or lactating.
• Men and women or reproductive potential who are following acceptable birth control methods (as determined by the treating physician, however abstinence is not an acceptable method).
• Patients who have previously been treated on Phase II drugs can be included if no long-term toxicity is expected, and the patient has been off the drug for four or more weeks with no significant post treatment toxicities observed
• Patients should have at least 4 \* 106 CD34+/kg peripheral stem cells collected. Whenever possible, 1 to 2 \* 106 CD34+/kg, for the first 10 patients and held for 1 year in case of graft failure. If graft failure does not occur in the first 10 patients, backup cells will not be required for subsequent patients.

You may not qualify if:

• Patients with impaired bone marrow reserve, as indicated by one or more of the following: Prior myeloablative therapies with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue Platelet count \< 100,000 cells/mm3 Hypocellular bone marrow Marked reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid) History of failed stem cell collection of \> 4\*106 CD34+/kg
• Prior radioimmunotherapy.
• Presence of central nervous system (CNS) lymphoma.
• Patients with chronic lymphocytic lymphoma.
• Patients with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related lymphoma.
• Patients with abnormal liver function: total bilirubin \> 1.5 mg/dl
• Patients with abnormal renal function: serum creatinine \> 1.6 mg/dl
• Patients who have received prior external beam radiation therapy to \>25% of active bone marrow (involved field or regional).
• Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.
• Corrected carbon monoxide diffusion in the lung (DLCO) \<50% and forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) \< 50% predicted.
• Cardiac ejection fraction (EF) \< 50% by 2-D Echogram.
• Pleural effusions.
• Prior radiation to lungs.
• Abnormal cytogenetics, filter in situ hybridization (FISH) (-5, -7, 11q23)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Biogen: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Chamoun K, Milton DR, Ledesma C, Young KH, Jabbour EJ, Alatrash G, Anderlini P, Bashir Q, Ciurea SO, Marin D, Molldrem JJ, Olson AL, Oran B, Popat UR, Rondon G, Champlin RE, Gulbis AM, Khouri IF. Allogeneic Transplantation after Myeloablative Rituximab/BEAM +/- Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-Up Results. Biol Blood Marrow Transplant. 2019 Jul;25(7):1347-1354. doi: 10.1016/j.bbmt.2019.02.022. Epub 2019 Mar 1.

  PMID: 30826465 DERIVED

• Chahoud J, Sui D, Erwin WD, Gulbis AM, Korbling M, Zhang M, Ahmed S, Alatrash G, Anderlini P, Ciurea SO, Oran B, Fayad LE, Bassett RL Jr, Jabbour EJ, Medeiros LJ, Macapinlac HA, Young KH, Khouri IF. Updated Results of Rituximab Pre- and Post-BEAM with or without 90Yttrium Ibritumomab Tiuxetan during Autologous Transplant for Diffuse Large B-cell Lymphoma. Clin Cancer Res. 2018 May 15;24(10):2304-2311. doi: 10.1158/1078-0432.CCR-17-3561. Epub 2018 Feb 23.

  PMID: 29476021 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Lymphoma

Interventions

ibritumomab tiuxetan; Rituximab; Carmustine; Etoposide; Cytarabine; Melphalan; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

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; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Issa Khouri, MD / Professor, Stem Cell Transplant
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-745-2803

Study Officials

• Issa F. Khouri, MD,BS

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: February 24, 2012
• Study Start: September 1, 2003
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: September 11, 2014
• Results First Posted: September 11, 2014

Record last verified: 2014-09

Locations

US (1)