Lenalidomide Therapy After Chemotherapy & Stem Cell Transplant in Treating Chemotherapy Resistan Non-Hodgkin Lymphoma

NCT01035463 | Completed Phase 1 Results DMC

• 4 other identifiers: 0446-08-FBNCI-2009-01436RV-LYM-PI-0328P30CA036727
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II trial studies the side effects and best dose of lenalidomide when given after combination chemotherapy with or without rituximab and stem cell transplant and to see how well it works in treating patients with non-Hodgkin lymphoma that has not responded to treatment or has returned after a period of improvement and is resistant to chemotherapy. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, may block cancer growth by targeting certain cells. Giving lenalidomide after combination chemotherapy with or without rituximab may work better in treating patients with non-Hodgkin lymphoma.

Conditions

Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Transformed Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of Lenalidomide (Phase I)

  The Maximum Tolerated Dose (MTD) is defined to be the dose cohort below which 3 out of 6 subjects experience dose limiting toxicities during cycle 1. Dose limiting toxicities graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Cycle 1, 28 days

Secondary Outcomes (2)

• Event-free Survival

  1 year

• Overall Survival

  1 year

Study Arms (1)

Treatment (stem cell transplantation)

EXPERIMENTAL

PRE-CONDITIONING (patients with CD20+ NHL): Patients receive rituximab IV per standard of care. PREPARATIVE REGIMEN: Patients receive carmustine IV on day -6, etoposide IV BID and cytarabine IV BID on days -5 through -2, and melphalan IV on day -1. AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION: Patients undergo stem cell infusion on day 0. MAINTENANCE THERAPY: Beginning approximately 100 days post-transplant, patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Lenalidomide; Drug: Melphalan; Biological: Rituximab

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous hematopoietic stem cell transplant

Also known as: Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation

Treatment (stem cell transplantation)

Carmustine DRUG

Given IV

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021

Treatment (stem cell transplantation)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (stem cell transplantation)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (stem cell transplantation)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (stem cell transplantation)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (stem cell transplantation)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

Treatment (stem cell transplantation)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persistent, or relapsed non-Hodgkin's lymphoma (NHL) (any histology) that is chemo-resistant (\< a partial response \[PR\]), subjects who have received \>= 3 prior chemotherapy regimens, or subjects with lymphomas that have a high relapse rate following autologous or syngeneic stem cell transplantation (transformed NHL, peripheral T-cell lymphoma \[PTCL\], mantle cell lymphoma, anaplastic lymphoma kinase \[ALK\]-negative anaplastic large cell lymphoma \[ALCL, alk neg\]), intermediate International Prognostic Index (IPI) or high risk IPI or subjects with a positive positron emission tomography (PET) scan prior to transplant, and otherwise eligible for transplantation with adequate end-organ function
• Subjects that relapse within one year of diagnosis
• Able to collect \>= 1.5 x 10\^6 CD34+/kg cell for transplantation
• Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 and platelet count \>= 60 K when maintenance lenalidomide is started (day 100 post-transplant)
• Subjects must have calculated creatinine clearance \>= 30 ml/min
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN
• Subjects who are seropositive because of hepatitis B virus vaccine
• Subjects must be willing to give written informed consent, and sign an institutionally approved consent form before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Able to adhere to the study visit schedule and other protocol requirements
• Expected survival duration of \>= six months
• Karnofsky performance status \>= 70
• Subjects \> age 60 or with clinical signs of heart disease must have ejection fraction \>= 45% left ventricular ejection fraction (LVEF) pre-transplant
• Subjects with clinical signs of pulmonary insufficiency must have diffusion capacity of the lung for carbon monoxide (DLCO) to be measured at \>= 50% of predicted value
• No serious disease or condition that, in the opinion of the investigator, would compromise the subject's ability to participate in the study

You may not qualify if:

• Chemosensitive NHL, except subjects receiving \>= 3 prior chemotherapy regimens, or subjects having transformed NHL, PTCL, mantle cell lymphoma (MCL) or ALCL, alk neg
• End-organ function not appropriate for transplantation
• Inability to collect adequate stem cells
• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type B (HBV) or C (HCV) or active hepatitis
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide)
• Known hypersensitivity to thalidomide or lenalidomide (if applicable)
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Any prior use of lenalidomide
• Concurrent use of other anti-cancer agents or treatments
• Serum creatinine \> 2.0 mg/dL or calculated creatinine clearance \< 30 ml/min
• Active infection at the start of lenalidomide
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
• History of life threatening or recurrent thrombosis/embolism; subjects may participate if they are adequately anticoagulated during the treatment
• Subject has \> grade 2 peripheral neuropathy within 14 days before enrollment

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, Lossos IS, Li J, Pietronigro D, Witzig TE. Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. Br J Haematol. 2013 Sep;162(5):639-47. doi: 10.1111/bjh.12449. Epub 2013 Jul 9.

  PMID: 23834234 DERIVED

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Lenalidomide; Melphalan; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Julie M Vose
• Organization: University of Nebraska Medical Center

jmvose@unmc.edu

402-559-3848

Study Officials

• Julie Vose, MD, MBA

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2009
• First Posted: December 18, 2009
• Study Start: November 12, 2009
• Primary Completion: July 27, 2017
• Study Completion: July 27, 2018
• Last Updated: October 10, 2023
• Results First Posted: November 8, 2019

Record last verified: 2023-09

Locations

US (3)