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

Primary Purpose

Mantle Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring CYCLOPHOSPHAMIDE (CYTOXAN), CYTARABINE (ARA-C), DOXORUBICIN/ADRIAMYCIN, PREDNISONE, RITUXIMAB, TOSITUMOMAB (BEXXAR), Iodine, VINCRISTIN, Lymphoma, Chemo-Radioimmunotherapy, Autologous Transplantation, Untreated, 11-095

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering at Basking Ridge
  • Memorial Sloan Kettering Cancer Center @ Suffolk
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering at Mercy Medical Center
  • Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.

Arm Description

This is a phase I/phase II multi-institution trial. The phase I part of the trial will determine the MTD of cytarabine. The phase II part of the trial will examine the efficacy of the proposed regimen by evaluating the 3-year event-free survival (EFS) in patients with untreated mantle cell lymphoma. All patients in the study in both phases will undergo induction and consolidation with R-CHOP 14R-HIDAC, followed by RIT/HDT/ASCR.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

3-year Event Free Survival (EFS)
in subsets of patients with Ki-67 ≥ 30%
rates of complete remission (CR)
as defined by CT, FDG-PET and histology
Determine 3 year overall survival (OS).
Defined as last known follow up or date of death - date of diagnosis.

Full Information

First Posted
November 29, 2011
Last Updated
August 14, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01484093
Brief Title
Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma
Official Title
Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma: A Phase I/II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 29, 2011 (Actual)
Primary Completion Date
August 11, 2023 (Actual)
Study Completion Date
August 11, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
GlaxoSmithKline

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
CYCLOPHOSPHAMIDE (CYTOXAN), CYTARABINE (ARA-C), DOXORUBICIN/ADRIAMYCIN, PREDNISONE, RITUXIMAB, TOSITUMOMAB (BEXXAR), Iodine, VINCRISTIN, Lymphoma, Chemo-Radioimmunotherapy, Autologous Transplantation, Untreated, 11-095

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
Arm Type
Experimental
Arm Description
This is a phase I/phase II multi-institution trial. The phase I part of the trial will determine the MTD of cytarabine. The phase II part of the trial will examine the efficacy of the proposed regimen by evaluating the 3-year event-free survival (EFS) in patients with untreated mantle cell lymphoma. All patients in the study in both phases will undergo induction and consolidation with R-CHOP 14R-HIDAC, followed by RIT/HDT/ASCR.
Intervention Type
Other
Intervention Name(s)
R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
Other Intervention Name(s)
HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL RESCUE (ASCR)Patients admitted to the hospital for high dose chemotherapy. The anticipated length of, stay is 3-4 weeks. 14 days ± 1 day following the administration of the therapeutic dose of Iodine 131 I, Tositumomab, patients will be admitted for high-dose chemotherapy. BEAM, will be administered
Intervention Description
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.
Primary Outcome Measure Information:
Title
maximum tolerated dose (MTD)
Description
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
Time Frame
1 year
Title
3 year Event Free Survival (EFS)
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
3-year Event Free Survival (EFS)
Description
in subsets of patients with Ki-67 ≥ 30%
Time Frame
3 years
Title
rates of complete remission (CR)
Description
as defined by CT, FDG-PET and histology
Time Frame
1 year
Title
Determine 3 year overall survival (OS).
Description
Defined as last known follow up or date of death - date of diagnosis.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Zelenetz, MD,PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering at Basking Ridge
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center @ Suffolk
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering at Mercy Medical Center
City
Rockville Centre
State/Province
New York
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
City
Sleepy Hollow
State/Province
New York
ZIP/Postal Code
10591
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33558202
Citation
Kumar A, Bantilan KS, Jacob AP, Park A, Schoninger SF, Sauter C, Ulaner GA, Casulo C, Faham M, Kong KA, Grewal RK, Gerecitano J, Hamilton A, Hamlin P, Matasar M, Moskowitz CH, Noy A, Palomba ML, Portlock CS, Younes A, Willis T, Zelenetz AD. Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):230-237.e12. doi: 10.1016/j.clml.2020.09.007. Epub 2021 Jan 1.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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