Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma

Mantle Cell Lymphoma Clinical Trial

Official title:

Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma: A Phase I/II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01484093
• Other study ID #: 11-095
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 29, 2011
• Est. completion date: August 11, 2023

Study information

• Verified date: August 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mantle cell lymphoma (MCL) is a rare and aggressive type of lymphoma, with only about 3,000 cases diagnosed per year. MCL is considered a difficult cancer to treat. This study is being done to better understand how to treat MCL.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: August 11, 2023
• Est. primary completion date: August 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Previously untreated advanced stage mantle cell lymphoma (Clinical stage 2 with abdominal involvement, stage 3 and stage 4).
• Histologic diagnosis confirmed by MSKCC pathologist as mantle cell lymphoma with Cyclin D1, or D2 and/or, D3 staining performed. Presence of measurable disease as determined by FDG-PET, CT, endoscopy, colonoscopy, or bone marrow biopsy.
• Ages 18-70.
• Transplant eligibility as confirmed by the Disease Management Team.
• KPS = 70%.

Adequate organ function:

• WBC ANC = 1000 cells/mcL and platelet count = 100,000 cells/mcL unless felt to be secondary to underlying mantle cell lymphoma at which any count is permissible.
• Adequate renal function as determined by Cr < or = to 1.5 mg/dL or 24 hr creatinine clearance = 50 ml/hr
• Adequate hepatic function as determined by total bilirubin < or = to 1.5x ULN (unless known Gilbert syndrome) and AST < or = to 5.0x ULN.
• Cardiac ejection fraction greater than or equal to 50% as determined by echocardiogram or MUGA.
• For patients = age 60, a stress echocardiogram will be required, with same requirements as above.
• DLCO greater than or equal to 50% as determined by pulmonary function tests performed prior to initiation of treatment.
• Patients with positive Hepatitis B serologies will be treated per institutional guidelines.

Exclusion Criteria:

• Prior treatment for mantle cell lymphoma, including more than 7 days of steroids, immunotherapy, radioimmunotherapy, or chemotherapy. This does not include patients who have initiated R-CHOP at an outside institution within 2 weeks of enrollment.
• Patients using > or = to 10mg/day of steroids for any chronic medical condition
• Pregnant or breast-feeding. Note: Pre-menopausal patients must have a negative, serum HCG within 14 days of enrollment,.
• HIV positive or Hepatitis C antibody positive.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Other:
• R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
INDUCTION: R-CHOP-14 CHEMOTHERAPY: 4 cycles every 2 weeks ± 1 day All patients in the study in both phases will undergo induction and consolidation with R-CHOP 14R-HIDAC, followed by RIT/HDT/ASCR. Patients will undergo restaging scans 12 to 14 days following completion of R-CHOP 14, with CT, and FDG-PET. Patients demonstrating at least a PR may proceed to consolidation with R-HIDAC. CONSOLIDATION: R- HIDAC CHEMOTHERAPY: 2 cycles every 3 weeks ± 2 days After R-HIDAC, restaging will occur 17-21 days post cycle 2 with CT scan (or FDG-PET, if this was positive following R-CHOP-14). Radioimmunotherapy Dosimetric dose is given approximately 4-5 weeks after completing cycle 2 of R-HIDAC. This is to be preferred 1 week post restaging scans 17-21 days post cycle 2 of RHIDAC, and up to 2 weeks post-scans will be acceptable only if required by 131 I Tositumomab availability.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York
United States	Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose (MTD)	of HIDAC. For this study the MTD will be the dose at which no more than one grade 3 CNS toxic event (defined by CTCAE 4.0 as severe neurologic symptoms limiting self care ADLs') up to two weeks following HIDAC occurs among a 6 patient cohort. Phase I	1 year
Primary	3 year Event Free Survival (EFS)	from 67% (historical control) to 80 % in all patients. The EFS interval starts at enrollment date, and an event is defined as death from any cause or progression of disease. Patients who have completed the ASCT but elect to be removed from the study or lost to follow-up by the end of the third year will be counted as events as well. Phase II	3 years
Secondary	3-year Event Free Survival (EFS)	in subsets of patients with Ki-67 = 30%	3 years
Secondary	rates of complete remission (CR)	as defined by CT, FDG-PET and histology	1 year
Secondary	Determine 3 year overall survival (OS).	Defined as last known follow up or date of death - date of diagnosis.	3 years

External Links

•   Memorial Sloan Kettering Cancer Center