Treatments > Refractory Disease (Overcoming Drug Resistance)

Last update: 08/21/2011

Protocols for Refractory Lymphomas: 
 
CLL | Aggressive/Diffuse | CNS Lymphoma | PMBCL | Follicular | Hodgkins | Mantle Cell | Marginal Zone/MALT | T-cell | NHL Unspecified | Low Counts and not Eligible for SCT

ALSO SEE:  About Drug Resistance | Treatments for Elderly | Eligibility Factors | Resources  Clinical Trials for Refractory Lymphomas  | Pipeline

Here we provide resources for patients and professionals to use when searching for information about treatment protocols that may help to overcome refractory disease - disease that is resistant, so far, to treatment. The references within are not necessarily up-to-date - so we have provided

It's most important to have expert guidance on treatments

One important goal for the patient is to understand the risks of the disease and the potential risks and benefits of the treatments under consideration. For example, it can be appropriate - even essential -  to use higher-risk aggressive therapies to treat high-risk disease in order to potentially eradicate the disease or produce a durable remission, but only if there is at least some data to show the goal of treatment is realistic for your diagnosis, and the risks are appropriate to your general health, age, treatment history, etc..

Consult with at least one outside expert to obtain opinion and rationales about your treatment options. Note: The rationales of experts can be more useful to you than opinion, especially when you receive different opinions from different experts.  

Clinical Trials? If the data for standard approaches specific to your diagnosis are not strong, consideration of investigational therapies becomes more reasonable. However, it does not follow that investigational therapies will always be safer or more effective than standard therapies. Therefore, you must read the Informed Consent documents carefully and seek objective opinions and the guidance of your treating physician. That said, you do not need your physician's permission to review clinical trials, contact clinical investigators, or participate in clinical trials. However, it is best to ask the investigator of the study to consult with your treating physician, and for you to consult independent experts regarding the potential risks and benefits of the investigational protocol you are considering.  See Locating Experts in the Field.

Questions you might ask the doctors you consult

If consulting an expert for the first time, prepare

* A concise overview of your treatment history  in timeline format.
* Your latest test results (Kab results, Imaging)
* Any secondary medical conditions
* Your age and general health

QUESTIONS:

* What is the most realistic goal of treatment? 
  
    Cure? Durable remission? Management with least toxicity? Pain relief? Other?  
 
* What percentage of patients - specific to my diagnosis, health, treatment history - have had a durable remission following the approach you are recommending?  What are the risks of this treatment?  

    May I have a copy of the published data you are basing the recommendation on?
 
* What is the prognosis for my diagnosis for management therapies - using the least toxic therapies, as needed? Is this approach realistic for my diagnosis and the clinical details and history of my case?  
 
* What protocols do you recommend and what advantages do each have relative to other treatment protocols?  
 
* What investigational protocols do you recommend, and why?

See Also:  Clinical-trials-for-me?  PDF

Protocols for Refractory Lymphomas by Disease Subtype

Note: This is a work in progress. We update this list in response to visitor . 

CLL- Relapsed / Refractory (or SLL)

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell Transplantation 

	overview for CLL - Medscape free login req.
	Mini allogeneic : Effective in Advanced Chronic Lymphocytic Leukemia  cancerconsultants.com

Chemotherapy-based protocols

	Bendamustine ncbi.nlm.nih.gov
	Nipent®/Cytoxan®/Rituxan® Shows High Activity in Previously Treated CLL or Low-Grade NHL  cancerconsultants.com
	Treanda (Bendamustine) Full Prescribing information: FDA as PDF file
	Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy. Haematologica. 2000 Dec;85(12):1268-70. PMID: 11114133
	Oxaliplatin, Fludarabine, Cytarabine, and Rituxan combination therapy  in patients with Richter's syndrome or fludarabine-refractory CLL.  J Clin Oncol. 2008 Jan 10;26(2):196-203. PMID: 18182662
	Rituximab with Cladribine  PMID: 16948126 The RC and RCC regimens were highly effective and well tolerated modalities of treatment in  heavily pretreated patients with indolent lymphoproliferative disorders.

Novel / Targeted Therapies

See also Pipeline
 

	Flavopiridol (Alvocidib) Induces Durable Responses in Relapsed CLL  with High-Risk Cytogenetic Abnormalities http://ash.confex.com/ash/2008/webprogram/Paper11242.html
	Oral Inhibitor of Syk - Fostamatinib Disodium (FosD)  http://ash.confex.com/ash/2008/webprogram/Paper5094.html
	Campath alone or combined with Rituxan for refractory CLL  mdanderson.org
	Maintenance alemtuzumab  PMID: 15160944 | Related articles
	Fenretinide* and Rituxan
	Revlimid (Lenalidomide) for CLL  leukemia-web.org

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CNS Lymphoma

Clinical Trial Search for CNS lymphoma ClinicalTrials.gov 

See also Pipeline

	Salvage Therapy With Temozolomide in Patient With Primary Brain Lymphoma  http://bit.ly/bH3IgR Temozolomide-based Clinical trials: http://bit.ly/cTcM0O Temozolomide as salvage treatment in primary brain lymphomas http://bit.ly/biziKd
	Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie Cellulaire. J Clin Oncol. 2008 Apr 14; PMID: 18413641

Primary Mediastinal B cell Lymphoma (PMBCL)

Clinical Trials: untreated: http://bit.ly/i4SQBN  | previously treated: http://bit.ly/i3CGVp 

See also Pipeline

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Aggressive (such as Diffuse Large B Cell)
 

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Clinical Trial Search for relapsed aggressive / DLBCL lymphoma
        ClinicalTrials.gov / ClinicalTrials.gov

Stem Cell Transplant (SCT) for relapsed aggressive lymphoma

	Autologous SCT: The International Prognostic Index predicts for outcome following autologous stem cell transplantation in patients with relapsed and primary refractory intermediate-grade lymphoma. Bone Marrow Transplant. 1999 Mar;23(6):561-7. PMID: 10217186 | Related articles
	Concurrent high-dose Rituxan before and after autologous stem-cell transplantation   PMID: 15800314

Chemotherapy-based protocols
 

	Bendamustine (Treanda)  PAL
	Bendamustine (Treanda) is effective in relapsed or refractory aggressive non-Hodgkin’s lymphoma  cancerconsultants.com
	High-Dose Celecoxib and Metronomic "Low-dose" Cyclophosphamide  clinicalcancerresearch
	Cyclophosphamide, Cytarabine and Methotrexate Regimen Followed  by Stem Cell Transplantation cancerconsultants.com
	NEW Dose-adjusted EPOCH jco.ascopubs.org (June 2008)
	Gallium nitrate, Rituxan and Dexamethasone  ASCO 2006
	Gemcitabine, Ifosfamide, Oxaliplatin and Rituximab (R-GIFOX)  ASH2005
	Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab  http://www.ncbi.nlm.nih.gov/pubmed/20578815
	High-Dose Celecoxib and Metronomic "Low-dose" Cyclophosphamide  clinicalcancerresearch
	ICE: Ifosfamide, carboplatin, etoposide PMID 12736224 | Abstracts
	ICE + Rituxan  PMID: 14739217 | Related articles | Free full text - Bloodjournal.org
	Ifosfamide, Epirubicin and Etoposide (IEV)  PMID: 15370212
	Metronomic chemotherapy (low/continuous dosing).
	Mitoxantrone, carboplatin, cytosine arabinoside, and methylprednisolone followed by  autologous peripheral blood stem cell transplantation (MiCMA): [effective]  PMID: 16419074
	Pixantrone Pixantrone: A New Agent with Activity in NHL cancerpublications.com  ClinicalTrials.gov  Pixantrone Combination Regimen Produces High Rates of Complete Remission  for Patients With Aggressive NHL Who Fail CHOP Therapy  Docguide.com
	R-GEMOX  Rituxan, gemcitabine, and oxaliplatin Medscape
	Sequential Doxorubicin and Topotecan in relapsed/refractory aggressive Burkitt's / DLBCL:  Results of CALGB 59906. Leuk Lymphoma. 2006 Aug;47(8):1511-7.  PMID: 16966261

Novel / Targeted therapies for aggressive lymphomas

See also Pipeline

	Oral Inhibitor of Syk - Fostamatinib Disodium (FosD)  http://ash.confex.com/ash/2008/webprogram/Paper5094.html
	Enzastaurin, May Slow Progression of DLBCL: Presented at ASH 2005  DocGuide.com   ClinicalTrials.gov
	Everolimus Active in Relapsed Aggressive Non-Hodgkin’s Lymphoma  Clinicaloptions.com  Target of rapamycin (mTOR) inhibitors in NHL Overall response rate: 32% Treatment well tolerated over extended duration Interim data support further investigation
	Fenretinide* clincal trials
	PTK787 for refractory or relapsed Diffuse Large Cell Lymphoma    Technical background on PTK787 AACR PDF  ClinicalTrials.gov
	Oral LY317615 Clinical Trials
	Revlimid (R) (lenalidomide) Medilexicon.com Revlimid (R) Demonstrates Activity against Relapsed/Refractory Aggressive  and Transformed NHL marketwatch.com
	YM155  ClinicalTrials.gov  | Background Cancer.gov   YM155 shows activity in relapsed and refractory DLBCL. abstract.asco.org  Targets Survivin - inhibitor of apoptosis proteins (IAPs)

	Radioimmunotherapy Radioimmunotherapy (Bexxar or Zevalin) PAL Clinical Trials
	Rituxan for aggressive non-Hodgkin's lymphomas relapsing after or refractory to auto SCT  PMID: 12416894

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Follicular lymphoma - Refractory / Transformed

Also see NHL unspecified  

Clinical Trial Search for relapsed follicular lymphoma ClinicalTrials.gov

Clinical Trial Search for relapsed follicular lymphoma ClinicalTrials.gov

Stem Cell Transplantation (SCT)

Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation   in relapsed advanced stage follicular lymphoma PMID: 18318762 | Related articles

Allogeneic type (from donor)  PAL

Non-Myeloablative (mini)   PAL "non-myeloablative" means pretreatment (conditioning phase of treatment) that has lower  toxicity and does not ablate (kill off) the myeloid cells in the marrow.  Often called a  mini-transplant.  "Allogeneic" means from a donor, in this case an HLA-identical sibling.   "Hematopoietic" means the process of forming blood cells from stem cells in the bone marrow.

Autologous cell transplantation  PubMed abstracts | PAL

High-dose therapy with autologous haematopoietic support in patients with transformed  follicular lymphoma: a study of 27 patients from a single center.   Ann Oncol. 1998 Aug;9(8):865-9. PMID: 9789609  PubMed | Abstracts

Radioimmunotherapy

	Radioimmunotherapy (Bexxar or Zevalin)    Clinical Trials | PAL
	Bexxar High-dose radioimmunotherapy (Bexxar) versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin's lymphoma: a multivariable cohort analysis. Blood. 2003 May 15 PMID: 12750161  PubMed  | Abstracts | PAL
	Bexxar for transformed fNHL
	Bexxar in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma:  Australian Multicenter Phase II Clinical Study. J Clin Oncol. 2006 Aug 28; PMID: 16940276
	Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with Zevalin, Review.  PMID: 10541376
	Zevalin for transformed fNHL

Chemotherapy-based protocols
 

	R-DHAOx - 95% (21 of 22) relapsed follicular lymphomas patients  realize durable remissions  http://bit.ly/6VASEB
	Bendamustine Plus Rituxan  PMID: 15908650 Bendamustine A recent study of the drug bendamustine shows it gives patients with advanced lymphoma  an option when other treatments fail. According to Oncologist Jonathan Friedberg,  M.D. of the University of Rochester, 70 percent of the patients in a trial study had  good responses to the treatment. He says 35 percent even went into remission.
	Fludarabine Related abstracts
	Metronomic chemotherapy (low/continuous dosing). oral low-dose PEP-C  PAL
	Phase II study of paclitaxel and estramustine in patients with recurrent and refractory NHL Cancer. 2004 Sep 28  PMID: 15455357
	Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory  Follicular Lymphoma   ClinicalTrials.gov   The purpose of this study is to evaluate the effectiveness and safety of combining bortezomib (Velcade) with rituximab, fludarabine, mitoxantrone, and dexamethasone in treating patients with follicular cell lymphoma.

Novel / targeted therapies

See also Pipeline

	Oral Inhibitor of Syk - Fostamatinib Disodium (FosD)  http://ash.confex.com/ash/2008/webprogram/Paper5094.html
	BMS 247550  ASCO 2005 | Clinical trial Given the novel mechanism, a Phase 2 study of BMS247550 in patients with drug resistant lymphoma was undertaken.
	Fenretinide*
	ONTAK  PMID: 12769354 | Abstracts
	Radiofrequency ablation of lymphoma. Blood. 2006 Feb 15;107(4):1624-6. Epub 2005 Oct 27  PMID: 16254135 | PAL
	Revlimid (Lenalidomide) a potent immune-modulator. Efficacy of lenalidomide oral monotherapy in relapsed or refractory indolent non-Hodgkin's lymphoma: Final results of NHL-001. abstract.asco.org  Oral lenalidomide monotherapy can produce durable responses with manageable side effects in relapsed or refractory indolent NHL
	Thalidomide use in patients with relapsed, refractory, low-grade lymphoma.  ASCO 2004 ~ Abstract  No:  6672  Maintenance therapy with Rituxan PMID: 16946304
	Radiotherapy  PMID: 12829665  PubMed | Abstracts
	Radioimmunotherapy Radioimmunotherapy (Bexxar or Zevalin)    Clinical Trials  | PAL

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Hodgkin's Lymphoma - Refractory / Relapsed

Clinical Trial Search for relapsed HL ClinicalTrials.gov

	Stem Cell Transplantation (SCT) PAL Allogeneic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin's lymphoma  Blood. 2009 Jun PMID: 19498021 Mini SCT (Reduced-intensity allogeneic stem cell transplantation) PubMed | Related articles
	Targeted / Novel therapies See also Pipeline Bispecific antibodies - (early investigational) novel investigative  treatment for refractory Hodgkin's disease  PubMed   Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease PubMed Fenretinide* Genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer PubMed Rituxan in lymphocyte predominance Hodgkin's disease: a case series PubMed Complete remissions with weekly dosing of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in a phase I dose-escalation study in patients with relapsed or refractory Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL).  abstract.asco.org SGN-35 was generally well tolerated and induced CRs in 7 of 8 evaluable pts at the two highest doses in heavily pretreated patients. Pivotal trials of this antibody-drug conjugate will initiate in early 2009.
	Chemotherapy-based PEND Chemotherapy in Patients with Refractory/Relapsed Hodgkin Lymphoma. Leuk Lymphoma. 2004;45(10):2079-2084. PMID: 15370253 | Related articles Ifosfamide, Carboplatin and Etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. PMID: 12736225 GDP - Gemcitabine, Dexamethasoneare and Cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group. Ann Oncol. 2003 Dec;14(12):1762-7. PMID: 14630682  Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin’s disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group http://annonc.oxfordjournals.org/content/14/12/1762.full.pdf+html [Efficacy of GDP regimen (gemcitabine, dexamethasone, and cisplatin) on relapsed or refractory aggressive non-Hodgkin's Lymphoma: a report of 24 cases]. http://www.ncbi.nlm.nih.gov/pubmed/19000458 INTERMEDIATE DOSE GEMCITABINE - CISPLATIN COMBINATION CHEMOTHERAPY (GEMCIS) WITHOUT TREATMENT DELAY FOR CYTOPENIA - A NEW STANDARD IN PRE-AUTOGRAFT REMISSION INDUCTION FOR RELAPSED OR REFRACTORY HODGKIN'S DISEASE? http://online.haematologica.org/eha13/browserecord.php?-action=browse&-recid=2173 Gemcitabine, Dexamethasone, and Cisplatin (GDP) Is An Effective and Well-Tolerated out-Patient Salvage Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and Hodgkin Lymphoma (HL) http://ash.confex.com/ash/2010/webprogram/Paper32244.html NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease PubMed
	Radiotherapy Phase I study of escalating doses of low-dose-rate, Loco-regional irradiation preceding Cytoxan-TBI (Total Body Irradiation) for patients with chemotherapy-resistant non-Hodgkin's or Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):166-71. PMID: 12909229

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Mantle Cell Lymphoma (MCL)

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Clinical Trial Search for relapsed MCL  ClinicalTrials.gov

Stem Cell transplants (SCT)

Tandem Transplants: Patients with mantle-cell lymphoma relapsing after autologous  stem cell transplantation may be rescued by allogeneic transplantation. Bone Marrow Transplant. 2000 Sep;26(6):677-9. PMID: 11035375

Allogeneic  SCT

	PAL
	Non-Myeloablative (mini)  "non-myeloablative" means pretreatment (conditioning phase of treatment) that has lower toxicity  and does not ablate (kill off) the myeloid cells in the marrow.  Often called a mini-transplant.   "Allogeneic" means from a donor, in this case an HLA-identical sibling.  "Hematopoietic" means  the process of forming blood cells from stem cells in the bone marrow.
	Allogeneic stem cell transplantation for mantle cell lymphoma--does it deserve a better look? Leuk Lymphoma. 2005 Feb;46(2):217-23. PMID: 15621804

Autologous SCT    

	PubMed abstracts | PAL
	Bexxar, High Dose with SCT  High-Dose Iodine-131-Labeled Rituxan and Autologous Stem  Cell Support Produces Long Lasting Effects in Patients with Mantle Cell Lymphoma Failing  Conventional Autologous Transplants  cancerconsultants.com

Chemotherapy-based protocols for relapsed MCL

	Bendamustine Plus Rituxan in Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma.  J Clin Oncol. 2005 May 20;23(15):3383-9. PMID: 15908650
	Gemcitabine and Oxaliplatinum an effective regimen in a patient with progressive refractory  MCL Leuk Lymphoma. 2004 Jun;45(6):1289-91. PMID: 15360015 | Related articles
	High (95%) Response Rates in Relapsed/Refractory Mantle Cell Lymphoma after R-HCVAD  Alternating with R-Methotrexate/Cytarabine (R-M-A). Session Type: Poster Session 650-II  ASH 2005

Targeted / Novel Therapies

 

	Oral Inhibitor of Syk - Fostamatinib Disodium (FosD)  http://ash.confex.com/ash/2008/webprogram/Paper5094.html
	BMS 247550  ASCO 2005 | Clinical trial The epothilones are a new class of natural products.
	CCI-779  Single-agent CCI-779 has substantial anti-tumor activity in relapsed MCL. This study  demonstrates that agents, which selectively target cellular pathways dysregulated in MCL cells  can produce therapeutic benefit. The high response rate warrants further studies of this agent in MCL,  but the high incidence of hematologic toxicity suggests that a lower dose should be explored.  CCI-779 at 25mg is currently being evaluated in MCL through an NCCTG trial Abstract #129  appears in Blood, Volume 104, issue 11, November 16, 2004  Also see: Clinical Trials
	Fenretinide*
	Maintenance therapy with Rituxan PMID: 16946304
	Radioimmunotherapy for MCL  PAL Zevalin® for Treatment of Patients with Relapsed and Refractory MCL.  Session Type: Poster Session 845-II  ASH 2004
	Revlimid  (Lenalidomide)  See Pipeline
	Targeting Angiogenesis in Mantle Cell Lymphoma   RT-PEPC ASH Thalidomide for MCL  PubMed | Abstracts  Thalidomide and Rituximab  cancerconsultants.com  10/04 Temsirolimus Shows Promise in Patients With Relapsed Mantle Cell Lymphoma:  Presented at ICML  pslgroup.com
	Velcade (Bortezomib) Multicenter Phase II Study of Bortezomib [Velcade] PMID: 17001068

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Marginal Zone (MZL) / MALT -
Richter's - Refractory / Transformed

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell Transplantation (SCT)

	PAL
	Autologous bone marrow transplantation for marginal zone non-Hodgkin's lymphoma. Leuk Lymphoma. 2004 Feb;45(2):315-20. PMID: 15101717 | Related abstracts

Chemotherapy-based [protocols for MZL

	HyperCVXD: PubMed | Abstracts
	Metronomic chemotherapy (low/continuous dosing). oral low-dose PEP-C   PAL
	Pixantrone Pixantrone: A New Agent with Activity in Non-Hodgkin's Lymphoma cancerpublications.com  ClinicalTrials.gov

Novel / Targeted therapies 

See also Pipeline

See also Follicular - Novel / Targeted

Radioimmunotherapy (Bexxar / Zevalin)

PAL

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T-cell - refractory / relapsed

Clinical Trials Search: ClinicalTrials.gov

See also Pipeline

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell transplants (SCT)

PAL

Allogeneic  SCT

Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. Br J Haematol. 2006 Jun 6; PMID: 16759221

Chemotherapy-based protocols
 

	EPOCH  PubMed | Abstracts
	Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients annonc.oxfordjournals.org
	Pegylated liposomal doxorubicin effective in poor prognosis CTCL  medwire-news

Targeted / Novel Treatments

	Effective treatment of a case of refractory mycosis fungoides with imatinib (Gleevec). Br J Haematol. 2006 May;133(4):353. No abstract available.  PMID: 16643439
	HuMax-CD4 Phase II cutaneous T-cell lymphoma (CTCL) studies - 55% of Higher Dose  Patients Achieve a Clinical Response in Primary Indication  prnewswire Apr 2004
	ONTAK (Denileukin diftitox) for refractory T-cell lymphomas  Denileukin diftitox (Ontak) for relapsed/refractory T-cell non-Hodgkin lymphoma interscience.wiley.com
	Forodesine HCl active single oral agent for advanced refractory CTCL  abstracts2view.com  Forodesine is a rationally designed, potent inhibitor of purine nucleoside phosphorylase (PNP)
	Histone deacetylase (HDAC) inhibitors:    Phase 2 Data for Romidepsin Showing Durable Response in Refractory  CTCL businesswire.com  "Romidepsin is a novel, cyclic peptide, pan-HDAC inhibitor under investigation for  hematologic malignancies" Phase II Trial of Oral Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) for  Refractory Cutaneous T-cell Lymphoma (CTCL). Blood. 2006 Sep 7; PMID: 16960145 | Related articles
	Lenalidomide / Revlimid  (investigational) PubMed articles | ClinicalTrials.gov A potent immune modulating agent.

Pralatrexate, a novel class of antifol  PMID: 17910632  All four patients with T-cell lymphoma (TCL) achieved a complete remission. Patients with  B-cell lymphoma achieved stable disease at best. For each TCL patient, the response  was more durable than their best response with chemotherapy. This early experience is  the first to document this unique activity of pralatrexate in TCL.

NEW: Pralatrexate and T-cell lymphoma

	Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Lymphoproliferative Malignancies  NCI  allos.com
	SGN-30 (Anti-CD30 mAb)  ASH 2006 | Clinical Trials

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Non-Hodgkin's Lymphoma (NHL) - unspecified

Clinical Trials Search: ClinicalTrials.gov

	Stem Cell transplant (SCT) Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients. Ann Oncol. 2001 Dec;12(12):1749-55. PMID: 11843254  PubMed | Abstracts Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant. Leuk Lymphoma. 2005 Mar;46(3):405-14. PMID: 15621831 | Related articles
	Allogeneic Hematopoietic Transplantation   PAL Non-Myeloablative (mini)
	Autologous cell transplantation  PubMed abstracts | PAL
	Radioimmunotherapy (Bexxar / Zevalin)  PAL
	Chemotherapy-based protocols Bendamustine (Treanda) Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma. Cancer. 2006 Aug 31; PMID: 16948126 The RC and RCC regimens were highly effective and well tolerated modalities of treatment in heavily pretreated patients with indolent lymphoproliferative disorders. DHAP | Eloxatin®  | EPOCH | ESHAP Fludarabine & Cyclophosphamide: FPD-R Preliminary Results of a Phase I/II Trial of BBR-2778 (Pixantrone) in Combination with Fludarabine, Dexamethasone, and Rituximab (FPD-R) in the Treatment of Patients with Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (NHL). Session Type: Poster Session 478-I  ASH 2004 Gemcitabine, cisplatin and methylprednisolone chemotherapy (GEM-P) is an effective regimen in patients with poor prognostic primary progressive or multiply relapsed Hodgkin's and non-Hodgkin's lymphoma. Br J Haematol. 2003 Mar;120(6):970-7  PMID: 12648066 | Abstracts Gemcitabine + Rituxan: a therapeutic option for elderly or frail patients with aggressive non Hodgkin's lymphoma? Leuk Lymphoma. 2005 Jan;46(1):71-5. PMID: 15621783  Irinotecan in Relapsed or Refractory Non-Hodgkin’s Lymphomas, Vol 16, No 8, Suppl 7 (August 2002)  cancernetwork.com Metronomic chemotherapy (low/continuous dosing).  oral low-dose PEP-C   PAL Liposomal vincristine (Onco TSC) in relapsed non-Hodgkin's lymphomas: early results of an ongoing phase II trial. Ann Oncol. 2000 Jan;11(1):69-72. PMID: 10690390  PubMed | Abstracts Multiple cycles [continuous dose] aggressive chemotherapy prior to autologous peripheral stem cell transplantation for lymphoma. Aust N Z J Med. 1997 Jun;27(3):323-9. PMID: 9227818  PubMed | Abstracts Oxaliplatin treatment in heavily pretreated patients with non-Hodgkin's lymphoma. Leuk Lymphoma. 2005 Oct;46(10):1437-40  PMID: 16252433 Paclitaxel: Phase II study of paclitaxel in combination with mitoxantrone and ifosfamide/mesna for patients with relapsed or refractory non-Hodgkin's lymphoma after failure to cytarabine/cisplatin combination. Invest New Drugs. 1999;17(2):187-92. PMID: 10638491  PubMed | Abstracts Pixantrone Pixantrone: A New Agent with Activity in Non-Hodgkin's Lymphoma cancerpublications.com  ClinicalTrials.gov  Pixantrone (BR 2778): Alternative to Doxorubicin?  - Might have similar activity against aggressive lymphomas as doxorubicin, with less cardio toxicity   Abstracts | Clinical trials Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or  refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 May 11; PMID: 17496309  Rituximab-EPOCH - an Effective Salvage Regime for Relapsed, Refractory, or Transformed B-Cell Lymphoma. Results of a Phase II Study. Year: 2001   Abstract No: 1157  Sensitization of ara-C-resistant lymphoma cells by a SATE pronucleotide analogue. Int J Cancer. 2003 Oct 20;107(1):149-54. PMID: 12925971 | Abstracts  Trofosfamide (palliative/elderly) as a salvage treatment with low toxicity in malignant lymphoma. A phase II study. Eur J Cancer. 1997 Mar;33(3):500-2. PMID: 9155539  PubMed | Abstracts
	Novel / Targeted therapies BMS 247550  ASCO 2005 | Clinical trial Elsamitrucin  Radiofrequency ablation of lymphoma. Blood. 2006 Feb 15;107(4):1624-6. Epub 2005 Oct 27  PMID: 16254135 | PAL Fenretinide* Promising Results For Patients With Aggressive, Recurrent Non-Hodgkin Lymphoma Using New Oral Drug (tipifarnib)  sciencedaily.com  "We were pleased with the results of this study because it demonstrates that tipifarnib has some single-agent activity in this aggressive tumor group," says Dr. Witzig. "Now we need to combine it with other effective agents to further enhance the activity for our patients." TRM-1 (TRAIL-R1 monoclonal antibody) in Subjects with Relapsed or Refractory NHL Condition: Lymphoma, Non-Hodgkin  clinicaltrials.gov Velcade approved for Multiple Myeloma will be available off label to patients with NHL  Abstracts YM155, a novel survivin suppressant, administered by 168 hour continuous infusion to patients with advanced solid tumors.  asco.org  2006    Two pts with chemotherapy refractory intermediate grade NHL had marked reduction of lymph nodes including one that was durable (PR reviewed independently). This pt went onto BMT and was in remission at the time of this submission.

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Lymphoma with low blood counts, and not eligible for SCT

Probably the most difficult circumstance is when your bone marrow function is low and you cannot tolerate treatment with the majority of agents for lymphoma.  The following agents and protocols were selected because they may be less harsh to immune function. This list is a work in progress, and is by no means complete. Please discuss with your doctors.
 

	Rituxan
	Interferon-alpha
	Denileukin diftitox (Ontak)    Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma. J Clin Oncol. 2004 Oct 15;22(20):4095-102. Epub 2004 Sep 7. PMID: 15353540
	T-cell therapy, if your doctor judges you can tolerate CVP as pretreatment (Fred Hutch) clinicaltrials.gov
	Velcade approved for Multiple Myeloma will be available off label to patients with NHL  Abstracts
	Bortezomib (Velcade) and Rituximab in Treating Patients With Non-Hodgkin's Lymphoma clinicaltrials.gov

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Resources

	Primary Chemo-Refractory Follicular Lymphoma: Treatment Approaches Post-BMT Author: Myron Czuczman, MD  cmelink.com
	Current Therapies in the Treatment of Non-Hodgkin's Lymphoma: Chemotherapy Richard I. Fisher, MD  Medscape (free login req.) - * Comprehensive *
	Sequencing of Therapies for Low-Grade Lymphomas  cancercare.org  Presenter: Peter Rosen, MD, Professor of Medicine, UCLA School of Medicine, Department of  Hematology and Oncology, Los Angeles, CA.
	Treatment of Persistent Lymphoma? - Response from Joseph A. Sparano, MD, 10/23/2001  Medscape (free login req.)
	"Thin" Decisions  Patient perspective on consulting experts and making treatment decisions
	Treatments of NHL (flowcharts) - MDACC  PDF
	About Transformation PAL

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Common Treatment Eligibility Factors

Be aware that one or more of the following may determine eligibility for some treatment protocols.  We recommend that you take an inventory of the following in order to make it easier to identify appropriate treatment protocols when consulting your doctor, outside experts, or investigators of investigational therapies.

	Diagnosis - lymphoma subtype (including phenotype markers, such as CD20, CD19, etc.)
	Treatment history - specific prior therapies or treatment types - may be required, or may exclude
	Bone marrow involvement with lymphoma (greater than 25% bilaterally for Bexxar/Zevalin)
	Bone marrow (Hematopoietic) function - measured by hemoglobin, lymphocytes, platelets, neutrophils
	Co morbidities - other conditions, such as heart (cardiovascular) disease, HIV, Hepatitis B/C, and other infections
	Kidney (Renal) function - measured by creatinine
	Liver (Hepatic) function  - measured by bilirubin, AST and ALT
	Lungs (Pulmonary) function - measured by a variety of tests or observation
	Neurological - such as history of seizures, CNS involvement
	Patient characteristics - age, gender, life expectancy, pregnancy status
	Performance status - as measured by Karnofsky standards

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About Drug Resistance

Potential methods to circumvent blocks in apoptosis in lymphomas. Curr Opin Oncol. 2002 Sep;14(5):490-503. Review. PMID: 12192267  PubMed

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ClinicalTrials.gov listings for refractory lymphomas  

Studies for Treatment of Refractory Lymphomas -
See Clinical Trials for Refractory Lymphomas