New: Fenretinide* and Rituxan*

Condition: B-cell lymphomas, including CLL

Rationale and goal:  "Drugs used in chemotherapy, such as fenretinide, 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, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving fenretinide together with rituximab may kill more cancer cells. 

PURPOSE: This phase I/II trial is studying the side effects and best dose of fenretinide and to see how well it works when given together with rituximab in treating patients with B-cell non-Hodgkin's lymphoma."

* Fenretinide (4-HPR) is a retinoid (vitamin A) analogue with antitumor and chemopreventive activities.  In a mouse model, Fenretinide showed synergy with Rituxan.  

TOPIC SEARCH Mechanisms - PubMed
TOPIC SEARCH Outcome data - Medscape | PubMed
TOPIC SEARCH Safety or Toxicity -  PubMed 

AME-133v  (modified anti-cd20 antibody)

Condition: Relapsed follicular lymphoma, or Refractory cd-20 positive NHL
with "low affinity form of Fc?RIIIa (F/F or F/V at position 158) as determined by FcR genotyping; " 

Rationale and goal:  The protein engineering of AME-133v is hypothesized to result in an anti-CD20 therapy with greater potency and efficacy in all patients, but particularly in genetically defined subpopulations that respond poorly to rituximab because they express a low affinity version of the Fc receptor on their immune effector cells. 

A monoclonal antibody that has increased binding for this receptor should be more effective in stimulating effector cell killing and thus improve response to the antibody. This study is designed to provide evidence of the safety and a preliminary understanding of the efficacy of AME 133v.. 

Also see: Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower 
concentrations and more effectively than rituximab - bloodjournal.org
TOPIC SEARCH Mechanisms - PubMed

HuMax-CD20 to Treat Early Stage Non-Hodgkin's Follicular Lymphoma

Condition: 

Rationale and goal:  The purpose of this trial is to determine the safety and efficacy of HuMax-CD20 as a treatment for Follicular Lymphoma (FL). 

AND:

HuMax-CD20 in Chronic Lymphocytic Leukemia 

Rationale and goal:  The purpose of this trial is to determine the safety and efficacy of HuMax-CD20 as a treatment for

Treanda™ (Bendamustine)

Condition: Non-Hodgkin's Lymphoma refractory to Rituxan

Rationale and goal:  This drug provides unique mechanisms that may overcome drug resistance.
 
TOPIC SEARCH Mechanisms - PubMed
TOPIC SEARCH Outcome data - ASCO | Medscape | PubMed
TOPIC SEARCH Safety or Toxicity - ASCO | PubMed 

Patient's story- Bendamustine overcomes refractory nhl
(Note: Each case and each person's lymphoma is unique.)
 

Pixantrone (BBR 2778) Versus Other Chemotherapeutic Agents 
 
Condition: Third line Relapsed Aggressive Lymphoma, Non-Hodgkin

Rationale and goal:  BBR 2778 is a novel aza-anthracenedione that has activity in experimental tumors and shows reduced potential for cardiotoxicity in animal models. This cytotoxic agent has structural similarities with mitoxantrone as well as general similarities with anthracyclines (such as the tricyclic central quinoid chromophore). 

BMS-247550 (epothilone) 

 
Conditions: Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma - 
including grade 3 follicular

Rationale and goal:  This drug provides unique mechanisms that may overcome drug resistance.

About BMS 247550 - The epothilones are a new class of natural products that induce hyperstabilization of polymerized tubulin in a fashion similar to that known for the taxanes. Unique to these compounds is their ability to overcome acquired drug resistance, regardless of whether it is related to over expression of p-glycoprotein  (MDR) or tubulin mutations.  Given the novel mechanism, a Phase 2 study of BMS247550 in patients with drug resistant  lymphoma was undertaken. ASCO 2005  
 
TOPIC SEARCH Mechanisms - PubMed
TOPIC SEARCH Outcome data - ASCO | Medscape | PubMed
TOPIC SEARCH Safety or Toxicity - ASCO | PubMed 

SDX-105 (Bendamustin/Treanda™) with Bortezomib (Velcade) 
 
Condition: Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or B-CLL

Rationale and goal:  Bendamustin and bortezomib have been shown to be effective in the treatment of patients with indolent Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). Both compounds appear not to be cross-resistant with prior therapy. Therefore, it is of interest to combine bendamustine and bortezomib in this patient population. 

Preliminary results from patients with multiple myeloma showed that the combination of bendamustine and bortezomib is efficacious and well tolerated. However, there are so far no data on this combination in patients with NHL or CLL.

MGCD0103 Given Three Times Weekly
 
Condition: Relapsed or refractory DLBCL or Follicular Lymphoma

Rationale and goal:  MGCD0103 is an experimental drug that belongs to a class of drugs known as the histone deacetylase inhibitors, which may restore normal control in cancer cells by affecting the genes and proteins that are being made. Laboratory tests show that this new investigational anti-cancer drug can slow down the growth of human cancer cells in mice; two clinical research studies are currently being performed in humans with cancer and a similar study is being performed in patients with the same disease.

Intratumoral Injection of CPG 7909, Combined With Low dose Local Radiation
 
NOTE:  Study closed as of March 2008,  might reopen before end of  year.

Condition:  low-grade B-cell lymphoma of any initial stage or mycosis fungoides of stage IB-IVA. B-cell lymphoma patients must have failed at least one prior treatment. Mycosis fungoides patients must have failed or have been intolerant of at least 2 topical or one systemic treatment.

Rationale and goal:  This is a single institution phase I / II trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas. 

Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.

Radiation and Bexxar

Condition: Previously treated follicular lymphoma with > 5 cm nodal tumors.

Rationale and goal:   "As the toxicity of Radiotherapy and Bexxar may not overlap, the combination of both may allow an increase in the therapeutic window for both radiotherapy and Bexxar therapy."

Combined Weekly Velcade and Bexxar 
 
Condition: Relapsed or Refractory Follicular Lymphoma

Rationale and goal:  The purpose of this study is to determine what dose of bortezomib in combination with tositumab I-131 is tolerable whether bortezomib and Tositumomab I-131 are effective in the treatment of relapsed or refractory non-hodgkin's lymphoma (NHL). Both agents are effective in treating relapsed and refractory NHL. Administer of the agents together may sensitize the cells to the radiation from Tositumomab I-131.

Cellular Immunotherapy using Genetically Modified Autologous CD20-specific CD8+ T Cell Clones

And: 

Cellular Immunotherapy With Autologous CD8+ Cytotoxic T Lymphocyte Clones After Chemo (Cyclophosphamide, Vincristine, and Prednisone)

Condition: Relapsed CD20+ follicular lymphoma
 
Rationale and goal:  Involves taking T-cells from individual patients, genetically altering the cells so that they target CD20 (a receptor found on many b-cell lymphomas and  normal b-cells), expanding the numbers, and re-infusing them into the patient following treatment with CVP, a combination of chemotherapy agents. 

Related article: Cancer T cell Therapy Expands ~ nature.com

Cellular Immunotherapy Using Autologous T Cell Cytolytic Clones Genetically Modified to be CD19-Specific and Express HyTK

Conditions:   CD19 expressing -  
   Follicular lymphoma (grade I, II or III), 
   Lymphoplasmacytoid lymphoma, 
   Marginal zone lymphoma (splenic, nodal or extranodal), 
   Mantle cell lymphoma, 
   Small lymphocytic lymphoma (SLL) /chronic lymphocytic leukemia (CLL)

Rationale and goal:  The purpose of this study is to assess the safety and feasibility of collecting T cells (blood cells that help fight infection) from subjects with this disease, genetically modifying them in the laboratory to recognize this type of lymphoma cell, and infusing them (giving them back by vein) to the same subjects. In addition to assessing the safety of delivering lymphoma-specific T cells, the safety of using the hormone IL-2 to support the survival of the infused T cells will also be studied. This study will also try to determine how long these cells stay in the blood stream after re-infusion and if they attack lymphoma cells once they are inside the body.

Lenalidomide (Revlimid)  
 
Condition: Relapsed or Refractory Hodgkin Disease

Rationale and goal: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer . 

...  evaluating the activity of Lenalidomide in patients with relapsed or refractory Hodgkin's lymphoma.

AND:
 

Lenalidomide (Revlimid)
 
Conditions: Refractory CLL or SLL

Rationale and goal: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer . 

... is studying how well lenalidomide works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that did not respond to treatment.


TOPIC SEARCH Mechanisms - PubMed
TOPIC SEARCH Outcome data - ASCO | Medscape | PubMed
TOPIC SEARCH Safety or Toxicity - ASCO | PubMed 
 

Rituxan and/or Lenalidomide (Revlimid)
 
Condition: follicular lymphoma - relapsed following Rituxan-based combination therapy

Rationale and goal:  Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. 

Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells.

TOPIC SEARCH: Mechanisms PubMed 
Outcome ASCO | Medscape | PubMed
Safety ASCO | PubMed 

CCI-779 and Rituxan
 
Condition: Relapsed or Refractory Mantle Cell lymphoma
 
Rationale and goal:  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 

Rituxan and Zevalin
 
Condition: Recurrent primary central nervous system (CNS) lymphoma

Rationale and goal:  Monoclonal antibodies, such as rituximab and yttrium Y 90 ibritumomab tiuxetan, can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells.

This clinical trial is studying how well giving Zevalin  together with Rituxan  works in treating patients with recurrent primary CNS lymphoma.

Rituxan and Zevalin and Cp7909 (an immune adjuvant) 
 
Condition: Refractory and relapsed NHL (including transformed follicular NHL, MALT, MCL, and DLBCL) 

Rationale and goal:  Biological therapies, such as CpG 7909, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as Rituxan and Zevalin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving CpG 7909 together with monoclonal antibodies may kill more cancer cells. 

PURPOSE: This phase I trial is studying the side effects and best dose of CpG 7909 when given together with rituximab (Rituxan) and yttrium Y 90 ibritumomab tiuxetan (Zevalin) in treating patients with non-Hodgkin's lymphoma that is recurrent or did not respond to previous treatment.
 

Yttrium-90 Radiolabeled Humanized Anti-Tac and Calcium-DTPA
 
Conditions: Tac-Expressing -
   Cutaneous T Cell Lymphoma; 
   Hodgkin's Disease; Neoplasm; 
   Non Hodgkin's Lymphoma; 
   Peripheral T Cell Lymphoma

Rationale and goal:  Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. 

... is studying the side effects and best dose of radiolabeled monoclonal antibody when given together with pentetic acid calcium and to see how well they work in treating patients with recurrent Hodgkin's lymphoma or non-Hodgkin's lymphoma.

LMP2a-Specific Cytotoxic T-Lymphocytes Following CD45 Antibody for Lymphoma
 
Condition: EBV-positive Lymphoma

Rationale and goal:  To determine the safety of autologous/syngeneic or allogeneic LMP-2 specific cytotoxic T-lymphocytes (CTL) in combination with CD45 monoclonal antibody (Mab) in patients with EBV positive Hodgkins disease (HD) or non Hodgkins lymphoma (NHL).

To obtain information on the expansion, persistence and anti-tumor effects of of autologous/syngeneic or allogeneic LMP-2 specific cytotoxic T-lymphocytes (CTL) given after lymphodepletion with CD45 monoclonal antibody (Mab) in patients with EBV positive Hodgkins disease or non Hodgkins lymphoma.

 

Vaccine with Interleukin-2 After Combination Chemotherapy
  
Condition: Previously treated, or untreated, Mantle Cell Lymphoma

Rationale and goal:  Vaccines made from gene-modified cells and a person's cancer cells may make the body build an effective immune response to kill cancer cells. Interleukin-2 (IL-2) may stimulate the white blood cells to kill cancer cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving vaccine therapy together with IL-2 after combination chemotherapy may be a more effective treatment for mantle cell lymphoma.

...  studying how well giving vaccine therapy together with IL-2 after combination chemotherapy works in treating patients with relapsed or de novo stage II, stage III, or stage IV mantle cell lymphoma

StemEx® Expanded Stem Cells Derived from Cord Blood to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy (ExCell) 

Conditions: 
   NHL with induction failure or relapse and sensitive to last chemotherapy course, and
   MDS with intermediate 2- or high-risk IPSS score. 

Rationale and goal:  The purpose of this study is to determine the efficacy and safety of transplanting StemEx® in patients with certain hematological malignancies. For these patients, it is suggested that StemEx® can improve upon the outcome of transplanting a single, un-manipulated cord blood unit by significantly increasing the number of stem/progenitor cells available to the patient.. 

Clinical Need: Only 30% of patients who could benefit from this procedure have an HLA-matched sibling. The lengthy search for a matched donor may critically delay transplantation. In addition, far fewer patients of racial minorities find suitable HLA-matched donors. Umbilical cord blood (UCB) has been increasingly used as an alternative source of stem cells; however, its use in adults and adolescent patients is limited due to insufficient cell dose required for satisfactory hematopoietic reconstitution.

Sponsor's website: http://stemexstudy.com/  

TOPIC SEARCH Cord blood derived Stem Cell transplantation - PubMed

added December 12, 2007

standard SCT with cord blood derived cells

Umbilical Cord Blood Transplantation 
 
Conditions: 
   High risk childhood non-Hodgkin's lymphoma; 
   Graft Versus Host Disease; 
   Leukemia; 
   Lymphoma; 
   Myelodysplastic (MDS) and myeloproliferative diseases

Rationale and goal:  Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

... studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.

SCT Donor Stem Cell Transplant
 
Conditions:  
   Childhood Hodgkin's lymphoma; 
   Childhood non-Hodgkin's lymphoma; Leukemia; 
   Lymphoma; myelodysplastic and myeloproliferative diseases - (eligible if relapse from Auto SCT)

Rationale and goal:  Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient’s immune system from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor’s T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving immunosuppressive therapy after the transplant may stop this from happening.

... studying how well donor bone marrow or peripheral stem cell transplant works in treating patients with relapsed hematologic cancer after treatment with chemotherapy and autologous stem cell transplant.

Vaccine Therapy  Following Chemotherapy and Peripheral Stem Cell Transplantation 
 
Condition: recurrent grade 1-3 follicular lymphoma

Rationale and goal:  Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Vaccine therapy may be an effective treatment for non-Hodgkin's lymphoma. 

... to study the effectiveness of vaccine therapy following chemotherapy and peripheral stem cell transplantation in treating patients who have non-Hodgkin's lymphoma.

Rituxan/BEAM versus Bexxar/BEAM with Autologous Stem Cell Transplantation

Conditions: Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-Cell NHL

Rationale and goal:  "The 0401 study addresses the issue of the best high-dose therapy regimen to use in a group of patients for whom autologous [harvested cells from self] transplantation is accepted as the treatment 
of choice – those with diffuse large cell lymphoma failing front-line therapy (either not achieving remission
or relapsing). The major cause of treatment failure after autotransplants in this situation is lymphoma recurrence. 

This study examine whether replacing Rituxan with and radiaoactive compound, Bexxar 
(which also targets CD20 cells) will decrease the relapse rate without increasing toxicity. "

also see protocol/0401 

AND: 

Bexxar followed by BEAM conditioning study and Autologous Stem Cell Transplant

Conditions: Relapsed Diffuse Large B-cell Lymphoma

Rationale and goal:   Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

... studying how well monoclonal antibody therapy, chemotherapy, and peripheral stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

AND:

BEAM+Bexxar & Autologous Stem Cell Transplant 

Conditions: Patients

Rationale and goal:  The purpose of this study is to assess the safety of 131I-anti-B1 Radioimmunotherapy when combined with high-dose BEAM or BEAC chemotherapy and hematopoietic stem cell transplantation. The study will also compare the difference in response rates and time to treatment failure between historical control patients receiving high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant and patients receiving radioimmunotherapy and high-dose BEAM or BEAC chemotherapy with autologous hematopoietic stem cell transplant. Patients will receive escalating doses of radioimmunotherapy with anti-B1 radiolabeled with 131Iodine, high-dose carmustine, etoposide, cytarabine and Melphalan (BEAM) chemotherapy, and autologous hematopoietic stem cell transplant.

AND:

Bexxar, Etoposide, and Cyclophosphamide Followed by Autologous Stem Cell Transplantation 
 
Conditions: Relapsed or Refractory non-Hodgkin's lymphoma 

Rationale and goal:  Radiolabeled monoclonal antibodies, such as Bexxar, can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, use different ways to stop cancer cells from dividing so they stop growing or die. Combining a radiolabeled monoclonal antibody with combination chemotherapy before autologous stem cell transplantation may kill more cancer cells. 

... to study the effectiveness of combining Bexxar with etoposide and cyclophosphamide followed by autologous stem cell transplantation in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

AND:

Bexxar Followed by Autologous Stem Cell Transplantation 
 
Condition: Older patients with relapsed or refractory NHL

Rationale and goal:   Radiolabeled monoclonal antibodies, such as Bexxar, can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, use different ways to stop cancer cells from dividing so they stop growing or die. Combining a radiolabeled monoclonal antibody with combination chemotherapy before autologous stem cell transplantation may kill more cancer cells. 

...  to study the effectiveness of combining iodine I 131 tositumomab with etoposide and cyclophosphamide followed by autologous stem cell transplantation in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.