About Lymphoma | Advocacy | Art | CAM | Clinical trials | Doctors - Experts - Centers | Guidelines at Diagnosis | News
Risk Factors | Side Effects | Statistics | Support | Symptoms | Tests | Treatments | Types of Lymphoma

Search Site         Guidelines at Diagnosis | About Clinical Trials            How to Help!

Patients Against Lymphoma

 

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 inquires


CLL- Relapsed / Refractory (or SLL)

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell Transplantation 
bullet

overview for CLL - Medscape free login req.

bullet

Mini allogeneic : Effective in Advanced Chronic Lymphocytic Leukemia  cancerconsultants.com

Chemotherapy-based protocols

bullet

Bendamustine ncbi.nlm.nih.gov    

bullet

Nipent®/Cytoxan®/Rituxan® Shows High Activity in Previously Treated CLL or Low-Grade NHL  cancerconsultants.com

bullet

Treanda (Bendamustine) Full Prescribing information: FDA as PDF file

bullet

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 

bullet

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  

bullet

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
 
bullet

Flavopiridol (Alvocidib) Induces Durable Responses in Relapsed CLL
 with High-Risk Cytogenetic Abnormalities
http://ash.confex.com/ash/2008/webprogram/Paper11242.html

bullet

Oral Inhibitor of Syk - Fostamatinib Disodium (FosD) 
http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

bullet

Campath alone or combined with Rituxan for refractory CLL  mdanderson.org

bullet

Maintenance alemtuzumab  PMID: 15160944 | Related articles

bullet

Fenretinide* and Rituxan

bullet

Revlimid (Lenalidomide) for CLL  leukemia-web.org 

Return to top


CNS Lymphoma

Clinical Trial Search for CNS lymphoma ClinicalTrials.gov 

See also Pipeline

bullet

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

bullet

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

 

Return to top 


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

bullet

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

bullet

Concurrent high-dose Rituxan before and after autologous stem-cell transplantation  
PMID: 15800314

Chemotherapy-based protocols
 

bullet

Bendamustine (Treanda)  PAL

bullet

Bendamustine (Treanda) is effective in relapsed or refractory aggressive non-Hodgkin’s lymphoma  cancerconsultants.com

bullet

High-Dose Celecoxib and Metronomic "Low-dose" Cyclophosphamide  clinicalcancerresearch

bullet

Cyclophosphamide, Cytarabine and Methotrexate Regimen Followed 
by Stem Cell Transplantation
cancerconsultants.com

bullet

NEW Dose-adjusted EPOCH jco.ascopubs.org (June 2008)

bullet

Gallium nitrate, Rituxan and Dexamethasone  ASCO 2006

bullet

Gemcitabine, Ifosfamide, Oxaliplatin and Rituximab (R-GIFOX)  ASH2005

bullet

Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab  http://www.ncbi.nlm.nih.gov/pubmed/20578815

bullet

High-Dose Celecoxib and Metronomic "Low-dose" Cyclophosphamide  clinicalcancerresearch

bullet

ICE: Ifosfamide, carboplatin, etoposide PMID 12736224 | Abstracts

bullet

ICE + Rituxan  PMID: 14739217 | Related articles | Free full text - Bloodjournal.org

bullet

Ifosfamide, Epirubicin and Etoposide (IEVPMID: 15370212

bullet

Metronomic chemotherapy (low/continuous dosing)

bullet

Mitoxantrone, carboplatin, cytosine arabinoside, and methylprednisolone followed by 
autologous peripheral blood stem cell transplantation (MiCMA): [effective]  PMID: 16419074

bullet

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 
bullet

R-GEMOX  Rituxan, gemcitabine, and oxaliplatin Medscape

bullet

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
bullet

Oral Inhibitor of Syk - Fostamatinib Disodium (FosD) 
http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

bullet

Enzastaurin, May Slow Progression of DLBCL: Presented at ASH 2005  DocGuide.com
  ClinicalTrials.gov

bullet

Everolimus Active in Relapsed Aggressive Non-Hodgkin’s Lymphoma  Clinicaloptions.com 
bullet Target of rapamycin (mTOR) inhibitors in NHL
bullet Overall response rate: 32%
bullet Treatment well tolerated over extended duration
bullet Interim data support further investigation 
 

bullet

Fenretinide* clincal trials

bullet PTK787 for refractory or relapsed Diffuse Large Cell Lymphoma 
 
bullet Technical background on PTK787 AACR PDF 
bullet ClinicalTrials.gov  
bullet

Oral LY317615 Clinical Trials

bullet

Revlimid (R) (lenalidomide) Medilexicon.com
bullet
Revlimid (R) Demonstrates Activity against Relapsed/Refractory Aggressive 
and Transformed NHL marketwatch.com

bullet

YM155  ClinicalTrials.gov  | Background Cancer.gov  

YM155 shows activity in relapsed and refractory DLBCL. abstract.asco.org 

Targets Survivin - inhibitor of apoptosis proteins (IAPs)

bullet

Radioimmunotherapy
bullet

Radioimmunotherapy (Bexxar or Zevalin) PAL

bullet

Clinical Trials

bullet

Rituxan for aggressive non-Hodgkin's lymphomas relapsing after or refractory to auto SCT 
PMID: 12416894

Return to top 


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)

bullet

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

Allogeneic type (from donor)  PAL

bullet

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

bullet

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

bullet

Radioimmunotherapy (Bexxar or Zevalin)

bullet

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

bullet

Bexxar for transformed fNHL

bullet

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 

bullet

Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with Zevalin, Review.  PMID: 10541376 

bullet

Zevalin for transformed fNHL

Chemotherapy-based protocols
 

bullet

R-DHAOx - 95% (21 of 22) relapsed follicular lymphomas patients  realize durable remissions  http://bit.ly/6VASEB
 

bullet

Bendamustine Plus Rituxan  PMID: 15908650
bullet

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.

bullet

Fludarabine Related abstracts

bullet

Metronomic chemotherapy (low/continuous dosing).
bullet

oral low-dose PEP-C  PAL

bullet

Phase II study of paclitaxel and estramustine in patients with recurrent and refractory NHL
Cancer. 2004 Sep 28  PMID: 15455357

bullet

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

bullet

Oral Inhibitor of Syk - Fostamatinib Disodium (FosD) 
http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

bullet

BMS 247550  ASCO 2005 | Clinical trial

Given the novel mechanism, a Phase 2 study of BMS247550 in patients with drug resistant lymphoma was undertaken

bullet

Fenretinide*

bullet

ONTAK  PMID: 12769354 | Abstracts

bullet

Radiofrequency ablation of lymphoma.
Blood. 2006 Feb 15;107(4):1624-6. Epub 2005 Oct 27  PMID: 16254135 | PAL

bullet

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

bullet

Thalidomide use in patients with relapsed, refractory, low-grade lymphoma.  ASCO 2004 ~ Abstract  No:  6672 

Maintenance therapy with Rituxan PMID: 16946304  

bullet

Radiotherapy  PMID: 12829665  PubMed | Abstracts

bullet

Radioimmunotherapy

Radioimmunotherapy (Bexxar or Zevalin)
   Clinical Trials  | PAL

Return to top


Hodgkin's Lymphoma - Refractory / Relapsed

Clinical Trial Search for relapsed HL ClinicalTrials.gov

bullet

Stem Cell Transplantation (SCT)
bullet

PAL

bullet

Allogeneic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin's lymphoma  Blood. 2009 Jun PMID: 19498021

bullet

Mini SCT (Reduced-intensity allogeneic stem cell transplantation) PubMed | Related articles

bullet

Targeted / Novel therapies

See also Pipeline
bullet

Bispecific antibodies - (early investigational) novel investigative 
treatment for refractory Hodgkin's disease  PubMed  

bullet

Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease PubMed

bullet

Fenretinide*

bullet

Genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer PubMed

bullet

Rituxan in lymphocyte predominance Hodgkin's disease: a case series PubMed

bullet

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.

bullet

Chemotherapy-based
bullet

PEND Chemotherapy in Patients with Refractory/Relapsed Hodgkin Lymphoma.
Leuk Lymphoma. 2004;45(10):2079-2084. PMID: 15370253 | Related articles

bullet

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

bullet

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 

bullet

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

bullet

NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease PubMed

bullet

Radiotherapy
bullet

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

Return to top


Mantle Cell Lymphoma (MCL)

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Clinical Trial Search for relapsed MCL  ClinicalTrials.gov

Stem Cell transplants (SCT)
bullet

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
bullet

 PAL

bullet

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.

bullet

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    
bullet

PubMed abstracts | PAL

bullet

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
bullet

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

bullet

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

bullet

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

 

bullet

Oral Inhibitor of Syk - Fostamatinib Disodium (FosD) 
http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

bullet

BMS 247550  ASCO 2005 | Clinical trial

The epothilones are a new class of natural products. 

bullet

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

bullet

Fenretinide*

bullet

Maintenance therapy with Rituxan PMID: 16946304  

bullet

Radioimmunotherapy for MCL 
bullet

PAL

bullet

Zevalin® for Treatment of Patients with Relapsed and Refractory MCL. 
Session Type: Poster Session 845-II  ASH 2004

bullet

Revlimid  (Lenalidomide)  See Pipeline

bullet

Targeting Angiogenesis in Mantle Cell Lymphoma  
bullet

RT-PEPC ASH

bullet

Thalidomide for MCL  PubMed | Abstracts 

bullet

Thalidomide and Rituximab  cancerconsultants.com  10/04

bullet

Temsirolimus Shows Promise in Patients With Relapsed Mantle Cell Lymphoma: 
Presented at ICML  pslgroup.com 

bullet

Velcade (Bortezomib)
bullet

Multicenter Phase II Study of Bortezomib [Velcade] PMID: 17001068 

Return to top


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

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell Transplantation (SCT)
bullet

PAL

bullet

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
bullet

HyperCVXD: PubMed | Abstracts

bullet

Metronomic chemotherapy (low/continuous dosing).

  • oral low-dose PEP-C   PAL

bullet

Pixantrone Pixantrone: A New Agent with Activity in Non-Hodgkin's Lymphoma cancerpublications.com 
ClinicalTrials.gov 

Novel / Targeted therapies 

See also Pipeline
bullet

See also Follicular - Novel / Targeted

Radioimmunotherapy (Bexxar / Zevalin)
bullet

 PAL

Return to top


T-cell - refractory / relapsed

Clinical Trials Search: ClinicalTrials.gov

See also Pipeline

Also see NHL - unspecified | PubMed | ClinicalTrials.gov

Stem Cell transplants (SCT)
bullet

PAL

Allogeneic  SCT

bullet

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

Chemotherapy-based protocols
 
bullet

EPOCH  PubMed | Abstracts

bullet

Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients annonc.oxfordjournals.org  

bullet

Pegylated liposomal doxorubicin effective in poor prognosis CTCL  medwire-news

Targeted / Novel Treatments

bullet

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

bullet

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

bullet

ONTAK (Denileukin diftitox) for refractory T-cell lymphomas 

Denileukin diftitox (Ontak) for relapsed/refractory T-cell non-Hodgkin lymphoma interscience.wiley.com

bullet

Forodesine HCl active single oral agent for advanced refractory CTCL  abstracts2view.com 

Forodesine is a rationally designed, potent inhibitor of purine nucleoside phosphorylase (PNP)

bullet

Histone deacetylase (HDAC) inhibitors 
bullet

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"

bullet

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 

bullet

Lenalidomide / Revlimid  (investigational) PubMed articles | ClinicalTrials.gov
A potent immune modulating agent. 

bullet

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.

bullet

NEW: Pralatrexate and T-cell lymphoma

bullet

Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Lymphoproliferative Malignancies  NCI  allos.com
 

bullet

SGN-30 (Anti-CD30 mAb)  ASH 2006 | Clinical Trials

Return to top


Non-Hodgkin's Lymphoma (NHL) - unspecified

Clinical Trials Search: ClinicalTrials.gov

bullet

Stem Cell transplant (SCT)
bullet

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

bullet

Allogeneic Hematopoietic Transplantation   PAL
bullet

Non-Myeloablative (mini) 

bullet

Autologous cell transplantation  PubMed abstracts | PAL

bullet

Radioimmunotherapy (Bexxar / Zevalin)
bullet

 PAL

bullet

Chemotherapy-based protocols
bullet

Bendamustine (Treanda)

bullet

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.

bullet

DHAP | Eloxatin®  | EPOCH | ESHAP

bullet

Fludarabine & Cyclophosphamide:

bullet

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

bullet

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

bullet

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 

bullet

Irinotecan in Relapsed or Refractory Non-Hodgkin’s Lymphomas, Vol 16, No 8, Suppl 7 (August 2002) 
cancernetwork.com

bullet

Metronomic chemotherapy (low/continuous dosing)
bullet

oral low-dose PEP-C   PAL

bullet

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

bullet

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

bullet

Oxaliplatin treatment in heavily pretreated patients with non-Hodgkin's lymphoma.
Leuk Lymphoma. 2005 Oct;46(10):1437-40  PMID: 16252433

bullet

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

bullet

Pixantrone Pixantrone: A New Agent with Activity in Non-Hodgkin's Lymphoma cancerpublications.com 
ClinicalTrials.gov 

bullet

Pixantrone (BR 2778): Alternative to Doxorubicin?  - Might have similar activity against aggressive lymphomas as doxorubicin, with less cardio toxicity   Abstracts | Clinical trials

bullet

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 

bullet

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 

bullet

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 

bullet

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

bullet

Novel / Targeted therapies
bullet

BMS 247550  ASCO 2005 | Clinical trial

bullet

Elsamitrucin 

bullet

Radiofrequency ablation of lymphoma.
Blood. 2006 Feb 15;107(4):1624-6. Epub 2005 Oct 27  PMID: 16254135 | PAL

bullet

Fenretinide*

bullet

Promising Results For Patients With Aggressive, Recurrent Non-Hodgkin Lymphoma Using New Oral Drug (tipifarnibsciencedaily.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."

bullet

TRM-1 (TRAIL-R1 monoclonal antibody) in Subjects with Relapsed or Refractory NHL
Condition: Lymphoma, Non-Hodgkin  clinicaltrials.gov

bullet

Velcade approved for Multiple Myeloma will be available off label to patients with NHL  Abstracts

bullet

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.

Return to top


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.
 

bullet

Rituxan

bullet

Interferon-alpha

bullet

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 

bullet

T-cell therapy, if your doctor judges you can tolerate CVP as pretreatment (Fred Hutch)
clinicaltrials.gov

bullet

Velcade approved for Multiple Myeloma will be available off label to patients with NHL  Abstracts

bullet

Bortezomib (Velcade) and Rituximab in Treating Patients With Non-Hodgkin's Lymphoma
clinicaltrials.gov 

Return to top


Resources

bullet
Primary Chemo-Refractory Follicular Lymphoma: Treatment Approaches Post-BMT Author: Myron Czuczman, MD  cmelink.com 
bullet
Current Therapies in the Treatment of Non-Hodgkin's Lymphoma: Chemotherapy
Richard I. Fisher, MD  Medscape (free login req.) - * Comprehensive *
bullet
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.
bullet
Treatment of Persistent Lymphoma? - Response from Joseph A. Sparano, MD, 10/23/2001 
Medscape (free login req.) 
bullet
"Thin" Decisions  Patient perspective on consulting experts and making treatment decisions
bullet
Treatments of NHL (flowcharts) - MDACC  PDF
bullet
About Transformation PAL

Return to top


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.

bullet

Diagnosis - lymphoma subtype (including phenotype markers, such as CD20, CD19, etc.)
 

bullet

Treatment history - specific prior therapies or treatment types - may be required, or may exclude
 

bullet

Bone marrow involvement with lymphoma (greater than 25% bilaterally for Bexxar/Zevalin)
 

bullet

Bone marrow (Hematopoietic) function - measured by hemoglobin, lymphocytes, platelets, neutrophils
 

bullet

Co morbidities - other conditions, such as heart (cardiovascular) disease, HIV, Hepatitis B/C, and other infections
 

bullet

Kidney (Renal) function - measured by creatinine
 

bullet

Liver (Hepatic) function  - measured by bilirubin, AST and ALT
 

bullet

Lungs (Pulmonary) function - measured by a variety of tests or observation
 

bullet

Neurological - such as history of seizures, CNS involvement 
 

bullet

Patient characteristics - age, gender, life expectancy, pregnancy status 
 

bullet

Performance status - as measured by Karnofsky standards

Return to top
 


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

Return to top

ClinicalTrials.gov listings for refractory lymphomas  

Studies for Treatment of Refractory Lymphomas -
See Clinical Trials for Refractory Lymphomas
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.