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

• Status: Terminated
• Trial end date: 2017-03-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Bellicum Pharmaceuticals
• Treatments: Alemtuzumab; Fludarabine; Fludarabine phosphate; Lenograstim; Melphalan; Methotrexate; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

1. Age >/= 18 years and

2. One of the following: a. Acute leukemia past first remission, in first or subsequent relapse, in second or greater remission. Patients in first remission should have with intermediate or high cytogenetic risk factors or flt3 mutation. Patients with relapsed disease. Patients with primary induction failure or relapse are eligible if they have < 10% bone marrow blasts, and no circulating blasts. b. Myelodysplastic syndrome with intermediate or high risk IPSS score, or treatment related MDS. c. CML resistant to tyrosine kinase treatment in a first or subsequent chronic phase or after transformation to accelerated phase or blast crisis.

3. 2 (continued): d. CLL, Lymphoma or Hodgkin's disease which has failed to achieve remission or recurred following initial chemotherapy. Patients must have at least a PR to salvage therapy, or low bulk untreated relapse (< 2 cm largest mass). e. Multiple myeloma which has relapsed or progressed and has achieved a partial response to salvage chemotherapy.

4. Patients must have one of the following donor types identified who are willing to donate peripheral blood: a. Related donor, 8/8 HLA-matched for HLA-A, -B, C and DR matched or, b. Matched Unrelated Donor (MUD), 8/8 HLA-matched for HLA A, B, C and DRB1 using allele level typing.

5. Performance score of at least 80% by Karnofsky.

6. Adequate major organ system function as demonstrated by: a. Creatinine < 1.8 mg/dl (or creatinine clearance > 40 ml/min) b. Bilirubin < 1.5 mg/dl except for Gilbert's disease c. ALT < 300 IU/ml d. Left ventricular ejection fraction equal or greater than 40%. e. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted, corrected for hemoglobin.

7. Patient or patient's legal representative, able to sign informed consent.

8. Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study 2006-0676.

9. The patient will need to be available for evaluation within 72 hours of symptoms of GVHD, occurring within 60 days of the planned donor lymphocyte infusion.

Exclusion Criteria:

1. Uncontrolled active infection.

2. Positive Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.

3. Women of child bearing potential not willing to use an effective contraceptive measure while on study.

4. Men not willing to use an effective contraception method while on study.

5. Known sensitivity to any of the products that will be administered during the study.

6. HIV seropositive.

7. Prior allogeneic transplant.