Treating High Risk Leukemia With CD40 Ligand & IL-2 Gene Modified Tumor Vaccine

NCT00058799 | Completed Phase 1

• 1 other identifier: H6408-Leu Leu
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is to determine the safety and dosage of special cells that may make the patients own immune system fight the leukemia. To do this we will put special genes into cells called fibroblasts that we have grown in the laboratory from a skin sample. The genes we put in these fibroblasts make them produce substances called CD40 Ligand (CD40L) and interleukin-2 (IL-2). These are natural substances that may help the immune system kill leukemia cells. Some of these fibroblasts producing CD40L and IL-2 mixed with a small quantity of the leukemic cells will then be put back into the body. Studies of cancers in animals and in cell lines suggest that substances like CD40L and IL-2 when mixed with cancer cells do help the body to recognize and kill these cancer cells. A treatment using IL-2 has been previously used in more than 40 children with neuroblastoma and similar treatments are being used in adults with other cancers. Some of the patients have shown significant tumor responses. However, we do not know if this treatment will work and we do not know the right amount of each of the special cells to use, so different patients will get different combination and numbers of cells. The purpose of this study is to learn the side effects and safe dosage of these special cells.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• • To determine the safety of up to six subcutaneous (SC) injections of autologous tumor cells admixed with autologous gene-modified skin fibroblasts. These fibroblasts are modified ex vivo to express the human CD40 Ligand (hCD40L) and interleukin-2 (hIL

  15 years

Study Arms (3)

Dose Level 1

EXPERIMENTAL

Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window.

Biological: Dose Level 1

Dose Level 2

EXPERIMENTAL

Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window.

Biological: Dose Level 2

Dose Level 3

EXPERIMENTAL

Patients are treated with up to six injections of their gene-modified CD40L and IL-2 skin fibroblasts and leukemic blasts, separated by one-two weeks in an immunological treatment window.

Biological: Dose Level 3

Interventions

Dose Level 1 BIOLOGICAL

Leukemic Blasts 2 x 10\^7; IL-2 Fibroblasts 2 x 10\^7; CD40L Fibroblasts 2 x 10\^5

Dose Level 1

Dose Level 2 BIOLOGICAL

Leukemic Blasts 2 x 10\^7; IL-2 Fibroblasts 2 x 10\^7; CD40L Fibroblasts 2 x 10\^5

Dose Level 2

Dose Level 3 BIOLOGICAL

Leukemic Blasts 2 x 10\^7; IL-2 Fibroblasts 2 x 10\^7; CD40L Fibroblasts 4.2 x 10\^7

Dose Level 3

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients less than or equal to 75 years old with lymphoid (pre-B, B, T, non B-, non T, or Burkitt if bone marrow blasts \> 20%) or acute myeloid leukemia (M0 to M7) or myelodysplastic syndrome and with: Disease that has entered remission with chemotherapy and/or bone marrow transplantation, but is considered to be at high risk of relapse. or Primary, or relapsed treatment-refractory disease who, at the time of reinjection of the tumor vaccine, are at a state of complete or partial cytological remission disease (\<20% blasts infiltrating the bone marrow) after a second/higher line of conventional and/or high dose chemotherapy.
• Patients must have a life expectancy of at least 10 weeks.
• Patients must have ECOG performance status of 0-2 as below:
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute neutrophil count \>500/mm3, absolute lymphocyte count \>200/mm3, and platelet count \>50,000/mm3.
• Patients must not have active GvHD at the time of protocol entry.
• Patient has not received high dose steroids within the last week or other immunosuppressive drugs within a week (or longer as indicated by the half life of the agent)
• Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic Septra.)
• Patients must not be HIV-positive.
• Patients must have adequate liver function (bilirubin\<1.5 mg% SGOT\<2x normal, normal prothrombin time).
• Patients must have transduced cells available that are demonstrably \>20% CD40L expressing fibroblasts and producing\>150 pg IL-2/10 6 cell/24 hr.
• Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
• Patient must not have received treatment with other investigational agents within the last 4 weeks.
• Patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.

You may not qualify if:

• Rapidly progressive/refractory disease (\>20% blasts infiltrating the bone marrow)
• Life expectancy \< 10 weeks
• Active infection
• Need for concomitant drugs except analgesics
• Pregnancy or lactation
• Seropositive for HIV

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (3)

Texas Children's Hospital GCRC

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Malcolm K Brenner, MD, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dist Serv Prof, Center for Gene Therapy

Study Record Dates

• First Submitted: April 11, 2003
• First Posted: April 15, 2003
• Study Start: June 1, 1999
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 21, 2020

Record last verified: 2020-01

Locations

US (3)