Zevalin-beam for Aggressive Lymphoma

• Sponsor: Sheba Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00491491
• Collaborator: City of Hope Medical Center (Other), Amsterdam UMC, location VUmc (Other), University of Göttingen (Other)
• Enrollment: 60
• Locations: 9
• Arms: 2
• Duration (Months): 92.1
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study hypothesis is that the addition of zevalin radioimmunotherapy to the conditioning regimen given prior to BEAM high-dose chemotherapy and autologous stem cell transplantation in patients with aggressive lymphoma will reduced disease recurrence rate and improve overall and disease-free survival.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: ibritumomab tiuxetan; Procedure: BEAM chemotherapy and autologous stem-cell transplantation	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: SPINOZA / שפינוזה. Study With Preparatory INduction Of Zevalin in Aggressive Lymphoma. A Randomized Phase 3 Study of BEAM Versus 90Yttrium Ibritumomab Tiuxetan (Zevalin) / BEAM in Patients Requiring Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Relapsed Diffuse Large B-cell Lymphoma
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Z-BEAM ibritumomab tiuxetan (zevalin) BEAM	Drug: ibritumomab tiuxetan; 0.4 mCi/kg; Other Names: zevalin ; Procedure: BEAM chemotherapy and autologous stem-cell transplantation
Active Comparator: standard BEAM standard BEAM chemotherapy	Procedure: BEAM chemotherapy and autologous stem-cell transplantation

Outcome Measures

Primary Outcome Measures

1. Overall Survival [2 years after transplantation]

   actuarial 2 year survival

Secondary Outcome Measures

1. Progression-free Survival [2 years after transplantation]

   actuarial 2-year PFS

2. Clinical Response [100 days after transplantation]

   complete response (CR) and partial response (PR) proportion at day 100,

3. Hematopoietic Recovery [100 days after transplantation]

   time to hematopoietic recovery

4. Grade III Toxicity [100 days after transplantation]

   incidence of infection, grade III-IV toxicities, treatment-related mortality

5. Secondary Malignancies [5 years after transplantation]

   incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with CD20 positive diffuse large B-cell lymphoma as confirmed by a pathological biopsy report.

2. Patients who are candidates for autologous stem-cell transplantation due to primary refractory or first relapse of disease.

3. Patients must have chemo-sensitive disease achieving at least partial response (Cheson 2007 criteria) to last chemotherapy.

4. Age ≥ 18 years and age ≤ 70

5. Patients with adequate autologous stem cell collection for transplantation (target ≥ 2.5 x 106 CD34+ cells/kg).

6. Patients must sign written informed consent.

7. Adequate birth control in fertile patients.

8. All prior chemotherapy completed at least three weeks before study treatment.

9. Marrow involvement less than 25% at transplantation, no limitation on blood counts (low platelet count allowed).

10. Negative HIV antibody.

Exclusion Criteria:

1. 1. Chemo-refractory disease as determined by less than partial response (Cheson 2007 Criteria) to last chemotherapy.

2. Two or more relapses after initial response to induction chemotherapy.

3. High-grade transformation from earlier diagnosis of low-grade lymphoma. Patients with "De Novo" Transformed DLBCL, defined as DLBCL only on lymph node biopsy and a discordant marrow with para-trabecular small cells at first diagnosis of lymphoma, are eligible if adherent all other selection criteria.

4. Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit.

5. Creatinine > 2.0 mg/dl.

6. ECOG Performance status > 2.

7. Uncontrolled infection.

8. Pregnancy or lactation.

9. Abnormal lung diffusion capacity (DLCO < 40% predicted).

10. Severe cardiovascular disease; New York Heart Association (NYHA) Functional Classification ≥2.

11. Active CNS disease involvement.

12. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated for Stage I or II cancers are eligible provided they have a life expectancy > 5 years in relation to this prior malignance. The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ cervical cancer.

13. Pleural effusion or ascites > 1 liter.

14. Known hypersensitivity to rituximab.

15. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate.

16. Prior radioimmunotherapy.

17. Prior autologous or allogeneic HSCT.

18. Active evidence of Hepatitis B or C infection; Hepatitis B surface antigen positive.

19. Patients who have had prior radiation to the lung will be excluded from the study, although mediastinal irradiation will be permitted if minimal lung is in the treatment volume.

20. Patients who have received >500cGy radiation to the kidneys will be excluded from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Scottsdale	Arizona	United States
2	City of Hope National Medical Center	Duarte	California	United States	91010-3000
3	Cedars Sinai Medical Center	Los Angeles	California	United States
4	Moffitt Cancer Center	Tampa	Florida	United States
5	Northwestern University	Chicago	Illinois	United States
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	Georg-August Universität	Göttingen		Germany
8	Chaim Sheba Medical Center	Tel Hashomer		Israel
9	VU Medical Center	Amsterdam		Netherlands

Sponsors and Collaborators

• Sheba Medical Center
• City of Hope Medical Center
• Amsterdam UMC, location VUmc
• University of Göttingen

Investigators

• Study Chair: Avichai Shimoni, MD, Chaim Sheba Medical Center, Tel Hashomer, Israel
• Study Chair: Amrita Krishnan, MD, City of Hope National Medical Center, Duarte, CA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Avichai Shimoni MD, Dr. Avichai Shimoni, Sheba Medical Center
• ClinicalTrials.gov Identifier: NCT00491491
• Other Study ID Numbers: SHEBA-07-4466-AN-CTIL
• First Posted: Jun 26, 2007
• Last Update Posted: Aug 31, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Dr. Avichai Shimoni MD, Dr. Avichai Shimoni, Sheba Medical Center: non-Hodgkin's lymphoma; autologous stem cell transplantation; radioimmunotherapy; zevalin
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin

Study Results

Participant Flow

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Period Title: Overall Study
STARTED	22	21
COMPLETED	22	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Z-BEAM	Standard BEAM	Total
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation	Total of all reporting groups
Overall Participants	22	21	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 95.5%	20 95.2%	41 95.3%
>=65 years	1 4.5%	1 4.8%	2 4.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	51	55
Sex: Female, Male (Count of Participants)
Female	16 72.7%	11 52.4%	27 62.8%
Male	6 27.3%	10 47.6%	16 37.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Israel	22 100%	21 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	actuarial 2 year survival
Time Frame	2 years after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
Number (95% Confidence Interval) [percentage of participants]	91 413.6%	62 295.2%

2. Secondary Outcome

Title	Progression-free Survival
Description	actuarial 2-year PFS
Time Frame	2 years after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
Number (95% Confidence Interval) [percentage of PARTICIPANTS]	59	37

3. Secondary Outcome

Title	Clinical Response
Description	complete response (CR) and partial response (PR) proportion at day 100,
Time Frame	100 days after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
Number [participants]	22 100%	20 95.2%

4. Secondary Outcome

Title	Hematopoietic Recovery
Description	time to hematopoietic recovery
Time Frame	100 days after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
Median (Full Range) [DAYS]	10	11

5. Secondary Outcome

Title	Grade III Toxicity
Description	incidence of infection, grade III-IV toxicities, treatment-related mortality
Time Frame	100 days after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
grade III toxicity	3 13.6%	4 19%
infection	6 27.3%	1 4.8%
none	13 59.1%	16 76.2%

6. Secondary Outcome

Title	Secondary Malignancies
Description	incidence of myelodysplastic syndrome (MDS), and secondary acute myelogenous leukemia (AML).
Time Frame	5 years after transplantation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Z-BEAM	Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation	standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
Measure Participants	22	21
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Z-BEAM		Standard BEAM
Arm/Group Description	ibritumomab tiuxetan (zevalin) BEAM ibritumomab tiuxetan: 0.4 mCi/kg BEAM chemotherapy and autologous stem-cell transplantation		standard BEAM chemotherapy BEAM chemotherapy and autologous stem-cell transplantation
All Cause Mortality
	Z-BEAM		Standard BEAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Z-BEAM		Standard BEAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		0/21 (0%)
Infections and infestations
JC virus encephalitis	1/22 (4.5%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Z-BEAM		Standard BEAM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/22 (27.3%)		1/21 (4.8%)
Infections and infestations
infection	6/22 (27.3%)	6	1/21 (4.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.