Lymphocytic B-Leukemia (B-CLL) w/Human IL-2 Gene Modified & Human CD40 Ligand-Expressing Autologous Tumor Cells (CLONTAK)

Baylor College of Medicine

Status and phase

Withdrawn

Phase 1

Conditions

CHRONIC LYMPHOCYTIC B-LEUKEMIA

Treatments

Biological: CD40L

Biological: immunotoxin dose

Biological: IL-2 secreting and hCL4OL-expressing autologous B-CLL cells

Biological: IL-2

Drug: ONTAK

Study type

Interventional

Funder types

Other

Identifiers

NCT00224354

17656

CLONTAK

Details and patient eligibility

About

In the laboratory, we will put a special gene into cancer cells that have been taken from the subject. This gene will make the cells produce interleukin 2 (IL-2), which may help the patient's immune system kill cancer cells. Also, we will use CD40 ligand (CD40L) with the IL-2. Studies of cancers in animals and in cancer cells that are grown in laboratories have suggested adding the CD40L helps the IL-2 work better. Some of these new cells will then be given back to the subject as a vaccine shot.

We believe that a part of the subject's immune system (cells called T-reg cells) might try to kill off these special cells. If the T-reg cells do that, the vaccine would not work as well or last as long. To try to avoid this, before the special cells are put back into the subject's body, we will give them an intravenous (IV) dose of IL-2 immunotoxin (called denileuk diftitox or ONTAK). ONTAK should get rid of some of the T-reg cells in the subject's body which should help the special cells work better and longer.

The purpose of this study is to learn the safety and cancer-fighting effects of using IL-2 with the vaccine.

Full description

This is a phase I trial to assess the safety of depleting regulatory T (Treg) cells using 1-3 doses of an interleukin-2 immunotoxin directed to the CD25 antigen (denileukin diftitox, ONTAK) in chronic lymphocytic leukemia (B-CLL) patients, followed by six subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L). Patients will receive a fixed dose (2 x 10e7) of IL-2 secreting B-cells together with 2 x 10e7 hCD40L expressing B-cells, representing a safe, well tolerated and immunogenic dose in our previous dose escalation study.

All eligible patients will be treated with six injections. Any patient whose disease regresses after the administration of 6 injections may be offered further injections of tumor vaccine if sufficient vaccine is available. There will be no use of placebo or control subjects.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Pre Inclusion Eligibility Criteria: Proof of B-CLL diagnosis not in Richter's transformation

Eligibility Criteria:

Manipulated B-CLL cells available (at least 6 injections)
B-CLL with measurable disease, not in Richter's transformation
Life expectancy greater than or equal to 10 weeks
ECOG 0-2 (see Section 4.3 of the full protocol for details)
Recovered from the toxic effects of all prior chemotherapy
Absolute neutrophil count (ANC) greater than or equal to 500/mL
Absolute lymphocyte count (ALC) greater than or equal to 200/mL
Hemoglobin greater than or equal to 8 g/dL
Platelet count greater than or equal to 50,000/mL
Total bilirubin less than or equal to 1.5mg/dL -SGOT less than or equal to 2 x Normal
Normal PTT -Creatinine less than 3 x Normal (age-related) or Creatinine clearance > 80mg/min/1.73m2
Serum albumin level greater than or equal to 3 g/dl
Must not have received treatment with other investigational agents within the last 4 weeks
Practicing appropriate birth control during the study and for 3 months after the study is concluded.

Exclusion criteria

Congestive heart failure
Significant arrythmia or history of myocardial infarction
Active CNS disease or a history of seizure
Active infection / receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole
Seropositive for HIV
Pregnancy or lactation / will not use birth control methods
Autoimmune disease (GvHD, immune thrombocytopenia-ITP or autoimmune hemolytic anemia-AIHA)
Receiving immunosuppressive drugs
Hypersensitivity to denileukin diftitox or any of its components: diphteria toxin, interleukin-2, or excipients