Donor Lymphocyte Infusion (DLI) of T-cells Genetically Modified With iCasp9 Suicide Gene

Summary

The goal of this clinical research study is to learn if giving genetically changed immune cells, called T-cells, after chemotherapy will improve the response to a stem cell transplant. The safety of this treatment will also be studied.

The process of changing the DNA (the genetic material in cells) of these T-cells is called "gene transfer." Researchers want to learn if these genetically-changed T-cells are effective in attacking cancer cells in patients with leukemia, MDS, lymphoma, Hodgkin disease, or MM, after they have received an allogeneic stem cell transplant.

The chemotherapy you will be given on study is fludarabine, melphalan, and alemtuzumab. These drugs are designed to stop the growth of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's stem cells.

Researchers also want to learn if giving AP1903 will help the symptoms of graft-versus-host disease (GvHD) that may occur after the T-cell infusion. GvHD occurs when donor cells attack the cells of the person receiving the stem cell transplant.

Conditions

• Leukemia
• Myeloma
• Myeloproliferative Diseases

Interventions

DRUG

Fludarabine

40 mg/m2 by vein on Days -6 to -3.

DRUG

Melphalan

140 mg/m2 by vein on Day -2.

DRUG

Alemtuzumab

50 mg by vein on Day -1.

PROCEDURE

Stem Cell infusion

Stem cell infusion on Day 0. Goal is to administer more than 3 x 10\^6 CD34+ cells/kg of peripheral blood progenitor cells (PBPC).

DRUG

Tacrolimus

Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml (target is 10 ng/ml) between Day +1 and Day +45. Tacrolimus is changed to oral dosing when tolerated. Tacrolimus tapering should start on approximately Day +35 with the intention for the patient to be completely off the drug by approximately Day +45.

DRUG

Mini Methotrexate

5 mg/m2 by vein on Days +1, +3, +6.

DRUG

G-CSF

5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until the absolute neutrophil count (ANC) is \> 500 x 10/L for 3 consecutive days.

PROCEDURE

Donor Lymphocyte Infusion (DLI)

iCasp9 (BPZ-1001)-Modified T-cells) of 3 X 10\^6/kg in 100 ml infused over approximately a one hour period between Day + 56 to Day +64.

DRUG

AP1903

0.4 mg/kg as a 2 hour infusion for patients that present with a clinical diagnosis of grade I GvHD. For patients with a clinical diagnosis of grade \> 2 GvHD, a single dose of AP1903 0.4 mg/kg as a 2 hour infusion will be administered. Patients who fail to achieve a complete response within 72 hours of an initial dose of AP1903, or within 48 hours of a second dose of AP1903, will be maintained on this dose for no less than 7 days. Patients who experience a partial response within 72 hours may receive a second dose of AP1903. Patients whose GvHD is progressing after 7 days, have no response by 14 days, or are not in a complete response at day 28 can receive secondary therapy.

DRUG

Methylprednisolone

1.6 mg/kg per day by vein divided in 2 to 3 daily doses. Patients whose GvHD resolves as defined by a complete response within 72 hours, would have steroids stopped immediately. Patients who fail to achieve a complete response within 72 hours of an initial dose of AP1903, or within 48 hours of a second dose of AP1903, will be maintained on this dose for no less than 7 days. Steroids can then be tapered as tolerated to no less than 0.6 mg/kg per day at day 28.

BEHAVIORAL

Questionnaire

Completion of a quality of life questionnaire that will take 10-15 minutes between Days + 28 and + 56, about twice a week until about 2 months after the T-cell infusion, and then 6 and 12 months after the stem cell transplant.

Sponsors & Collaborators

• Bellicum Pharmaceuticals

  collaborator INDUSTRY

• M.D. Anderson Cancer Center

  lead OTHER

Principal Investigators

• Richard E. Champlin, MD, BS · M.D. Anderson Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-12-27

Primary Completion

2017-03-07

Completion

2017-03-07

FDA Drug

Yes

Countries

• United States

Study Locations