Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

NCT00078949 | Completed Phase 3 Results DMC

• 3 other identifiers: LY12CAN-NCIC-LY12CDR0000353203
• Study Type: interventional
• Target: 849
• Locations: 3 countries
• Sites: 27

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation. Rituximab was added to both salvage treatment arms for CD20+ patients in a protocol amendment in 2005.

Conditions

Lymphoma

Keywords

anaplastic large cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; angioimmunoblastic T-cell lymphoma

Outcome Measures

Primary Outcomes (3)

• Response Rate of Patients After 2 Courses of Chemotherapy

  The overall response rate by arm is calculated as total number of responders (CR + CRu + PR) / (all patients in the ITT analysis population).

  After 2 cycle of treatment

• Transplantation Rate of Patients After 2 Courses of Chemotherapy

  Transplantation rate is defined as the number of patients who respond sufficiently to protocol salvage chemotherapy to be planned for transplantation minus those who do not meet the endpoint of successful transplantation, divided by the number of all randomized patients

  During period 1 (salvage chemotherapy)

• Event-free Survival of Patients on Maintenance Randomization (Period 2)

  Number of patients who develop EFS event during maintenance randomization (period 2)

  during the period 2 (up to10 years)

Secondary Outcomes (1)

• Toxic Effect

  48 months

Study Arms (4)

Salvage arm I

EXPERIMENTAL

Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8.

Drug: cisplatin; Drug: dexamethasone; Drug: gemcitabine hydrochloride

Salvage arm II

EXPERIMENTAL

Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2.

Drug: cisplatin; Drug: cytarabine; Drug: dexamethasone

Maintenance arm I

EXPERIMENTAL

Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.

Biological: rituximab

Maintenance arm II

NO INTERVENTION

Patients undergo observation only.

Interventions

rituximab BIOLOGICAL

Given IV

Maintenance arm I

cisplatin DRUG

Given IV

Salvage arm I; Salvage arm II

cytarabine DRUG

Given IV

Salvage arm II

dexamethasone DRUG

Given IV

Salvage arm I; Salvage arm II

gemcitabine hydrochloride DRUG

Given IV

Salvage arm I

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes: * Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma) * Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue \[MALT\] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse * Must be histologically confirmed * No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse * Peripheral T-cell lymphoma * Anaplastic large cell lymphoma * Small noncleaved Burkitt-like lymphoma * T-cell or B-cell lineage confirmed by immunohistochemistry * Clinically or radiologically documented disease meeting either of the following criteria: * Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI * Lymph nodes must be \> 1.5 cm by physical exam or CT scan * Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI * Bone lesions are not considered measurable * Evaluable disease, defined as only nonmeasurable disease, including any of the following: * Marrow infiltration * Cytology-confirmed ascites or effusions * Bony involvement * Enlarged liver or spleen * Unidimensionally measurable intrathoracic or abdominal masses * Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine * No uncontrolled CNS involvement by lymphoma * No CNS disease at time of relapse * CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained PATIENT CHARACTERISTICS: Age * 16 to 65 Performance status * ECOG 0-3 Life expectancy * At least 12 weeks Hematopoietic * Absolute granulocyte count ≥ 1,000/mm\^3 * Platelet count ≥ 75,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma) * Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection) Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * No significant cardiac dysfunction or cardiovascular disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Willing to complete quality of life questionnaires * HIV negative * No active, uncontrolled bacterial, fungal, or viral infection * No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix * No other concurrent serious illness or medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * See Chemotherapy * Prior rituximab allowed Chemotherapy * See Disease Characteristics * At least 4 weeks since prior IV chemotherapy * No prior high-dose chemotherapy with stem cell transplantation Endocrine therapy * No concurrent corticosteroids except for physiologic replacement Radiotherapy * At least 4 weeks since prior radiotherapy and recovered * Exceptions may be made for low-dose, non-myelosuppressive radiotherapy * No prior radiotherapy to more than 25% of functioning bone marrow * Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy Surgery * At least 2 weeks since prior major surgery Other * No other concurrent anticancer therapy * No other concurrent experimental agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (27)

Rush-Presbyterian-St. Luke's Medical Centre

Chicago, Illinois, 60612, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Cincinnati, Barrett Cancer Centre

Cincinnati, Ohio, 45219, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

QEII Health Sciences Center

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (7)

• Gupta A, Hay AE, Crump M, Djurfeldt MS, Zhu L, Cheung MC, Shepherd LE, Chen BE, Booth CM. Contact Days Associated With Cancer Treatments in the CCTG LY.12 Trial. Oncologist. 2023 Sep 7;28(9):799-803. doi: 10.1093/oncolo/oyad128.

  PMID: 37226534 BACKGROUND

• Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. doi: 10.1200/JCO.2013.53.9593. Epub 2014 Sep 29.

  PMID: 25267740 RESULT

• Gupta A, Thomas T, Hay AE, Crump M, Djurfeldt MS, Cheung MC, Prica A, Shepherd LE, Chen BE, Booth CM. The association of health care contact days with economic measures in the CCTG LY.12 trial. Oncologist. 2025 Jun 4;30(6):oyaf165. doi: 10.1093/oncolo/oyaf165.

  PMID: 40503814 DERIVED

• Assouline S, Li S, Gisselbrecht C, Fogarty P, Hay A, van den Neste E, Shepherd LE, Schmitz N, Baetz T, Keating A, Robinson S, Seftel M, Stelitano C, Djurfeldt MS, Meyer R, Chen BE, Crump M. The conditional survival analysis of relapsed DLBCL after autologous transplant: a subgroup analysis of LY.12 and CORAL. Blood Adv. 2020 May 12;4(9):2011-2017. doi: 10.1182/bloodadvances.2020001646.

  PMID: 32396614 DERIVED

• Bosch M, Akhter A, Chen BE, Mansoor A, Lebrun D, Good D, Crump M, Shepherd L, Scott DW, Stewart DA. A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma. Haematologica. 2018 Feb;103(2):288-296. doi: 10.3324/haematol.2017.179309. Epub 2017 Nov 2.

  PMID: 29097500 DERIVED

• Davison K, Chen BE, Kukreti V, Couban S, Benger A, Berinstein NL, Kaizer L, Desjardins P, Mangel J, Zhu L, Djurfeldt MS, Hay AE, Shepherd LE, Crump M. Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Ann Oncol. 2017 Mar 1;28(3):622-627. doi: 10.1093/annonc/mdw653.

  PMID: 27993811 DERIVED

• Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12. Blood. 2015 Aug 6;126(6):733-8. doi: 10.1182/blood-2015-01-622084. Epub 2015 Jun 24.

  PMID: 26109202 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large-Cell, Anaplastic; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Immunoblastic Lymphadenopathy

Interventions

Rituximab; Cisplatin; Cytarabine; Dexamethasone; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Deoxycytidine

Results Point of Contact

• Title: Seninor Biostatistician for LY12
• Organization: NCIC

bechen@ctg.queensu.ca

613-533-6000

Study Officials

• Michael R. Crump, MD, FRCPC

  Princess Margaret Hospital, Canada

  STUDY CHAIR

• Massimo Federico, MD

  Azienda Ospedaliero-Universitaria di Modena

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2004
• First Posted: March 9, 2004
• Study Start: August 27, 2003
• Primary Completion: July 29, 2013
• Study Completion: December 1, 2018
• Last Updated: August 23, 2023
• Results First Posted: October 21, 2014

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (21); US (5); AU (1)