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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01484093
First received: November 29, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Other: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma: A Phase I/II Trial

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose (MTD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    in subsets of patients with Ki-67 ≥ 30%

  • rates of complete remission (CR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    as defined by CT, FDG-PET and histology

  • Determine 3 year overall survival (OS). [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Defined as last known follow up or date of death - date of diagnosis.


Estimated Enrollment: 96
Study Start Date: November 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.
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.
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.
Other Names:
  • 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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01484093

Locations
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, United States, 07920
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
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, United States, 10591
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
GlaxoSmithKline
Investigators
Principal Investigator: Andrew Zelenetz, MD,PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01484093     History of Changes
Other Study ID Numbers: 11-095
Study First Received: November 29, 2011
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CYCLOPHOSPHAMIDE (CYTOXAN)
CYTARABINE (ARA-C)
DOXORUBICIN/ADRIAMYCIN
PREDNISONE
RITUXIMAB
TOSITUMOMAB (BEXXAR)
Iodine
VINCRISTIN
Lymphoma
Chemo-Radioimmunotherapy
Autologous Transplantation
Untreated
11-095

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014