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

Phase 1

Completed

• Conditions: Lymphoma
• Interventions: 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

• Registration Number: NCT01538472
• Lead Sponsor: M.D. Anderson Cancer Center

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.

Detailed Description

BEAM chemotherapy is the standard treatment for lymphoma. BEAM is a combination of chemotherapy drugs (carmustine, cytarabine, etoposide, and melphalan). Rituximab is an antibody made from human and mouse proteins. It reacts with a certain molecule on the surface of lymphoma cells and helps the body's immune system destroy the lymphoma cells. 90Y Zevalin is ...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2003-09
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Study First Submitted: 2012-02-20
• Study First Submitted QC: 2012-02-23
• Study First Posted: 2012-02-24
• Status Verified: 2014-09
• Results First Submitted: 2014-09-04
• Results First Submitted QC: 2014-09-04
• Last Update Submitted: 2014-09-04
• Results First Posted: 2014-09-11
• Last Update Posted: 2014-09-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Relapsed CD20-positive B-cell non-Hodgkin's lymphoma (NHL) (demonstrated in lymph nodes or bone marrow), chemosensitive (at least Partial Remission (PR)).
2. 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.
3. No prior radioimmunoconjugate therapy.
4. If patients had prior radiation, this should have not involved more than 25% of the bone marrow.
5. An IRB-approved signed informed consent.
6. Age: 18 to 65 years of age.
7. 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.
8. Patients determined to have <10% bone marrow involvement with lymphoma within four weeks before stem cell collection as defined by bilateral aspirates and biopsies.
9. Prestudy performance status of 0, 1, or 2 according to the World Health Organization (WHO).
10. Female patients included must not be pregnant or lactating.
11. 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).
12. 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
13. 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.

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Exclusion Criteria

1. 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
2. Prior radioimmunotherapy.
3. Presence of central nervous system (CNS) lymphoma.
4. Patients with chronic lymphocytic lymphoma.
5. Patients with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related lymphoma.
6. Patients with abnormal liver function: total bilirubin > 1.5 mg/dl
7. Patients with abnormal renal function: serum creatinine > 1.6 mg/dl
8. Patients who have received prior external beam radiation therapy to >25% of active bone marrow (involved field or regional).
9. Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives.
10. Corrected carbon monoxide diffusion in the lung (DLCO) <50% and forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% predicted.
11. Cardiac ejection fraction (EF) < 50% by 2-D Echogram.
12. Pleural effusions.
13. Prior radiation to lungs.
14. Abnormal cytogenetics, filter in situ hybridization (FISH) (-5, -7, 11q23)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Y Zevalin + BEAM	Y Zevalin	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.
Y Zevalin + BEAM	VP -16	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.
Y Zevalin + BEAM	G-CSF	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.
Y Zevalin + BEAM	In Zevalin	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.
Y Zevalin + BEAM	Stem Cell Infusion	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.
Y Zevalin + BEAM	Rituxan	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.
Y Zevalin + BEAM	BCNU	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.
Y Zevalin + BEAM	Ara-C	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.
Y Zevalin + BEAM	Melphalan	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.

Primary Outcome Measures

Name	Time	Method
3-Year Overall Survival	3 years	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.
Overall Survival Median	Participant followed from baseline treatment to 5 years, with study total period 8 years (study duration)	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.

Trial Locations

Locations (1)

UT MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States