MDACC Study Summary 2004-0069

Study Summary
No. 2004-0069:.......Melanoma......Patrick Hwu......Melanoma Medical Oncology

Study Summary Title



Study Summary Number:	2004-0069

Study Title:	Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma

Physician

New Patient Referral



Name:	Patrick Hwu	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Melanoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2921 Contact us about clinical trials

General Information



Disease Group:	Melanoma	Supported By:	N/A

Phase of Study:	Phase II	Return Visit:	Participants must return every 3 - 4 weeks for the first 2 months after treatment. Then, every 1-3 months for the next 10 months.

Treatment Agents:	Cyclophosphamide Filgrastim Fludarabine Interleukin-2 Mesna Ondansetron Hydrochloride Pegfilgrastim	Home Care:	None

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	Participants will be in the hospital for approximately 7 days each course for 2 courses of high dose IL-2 given at 3 to 4 week intervals.

Description/
Intervention:

The goal of this clinical research study is to learn if a vaccine prepared from
special blood cells (dendritic cells) will improve the function of fighting
immune cells (T cells) specific for melanoma. These special blood cells and
immune cells will be taken from patient's blood and tissue and grown in the
laboratory and then given back to the patient. Researchers will also study the
ability of these cells to shrink or slow the growth of the metastatic melanoma
when given with chemotherapy and Interleukin-2 (IL-2). Researchers will also
study if this combination will help to control the disease if there is a BRAF
mutation of the melanoma.

Study Objectives / Outcomes

The primary objective will be to determine whether patients receiving adoptively transferred, tumor antigen-specific T cells in combination with dendritic cells and high dose IL-2 have sustained persistence of infused T cells compared to patients treated with T cells and high dose IL-2 alone.

Secondary endpoints will include evaluations for tumor response and studies to determine whether dendritic cells enhance the infused T cells' anti-tumor activity and their ability to migrate to the tumor site. In addition, we will evaluate the characteristics of the infused T cells that correspond with effectiveness in vivo.

In a separate cohort (Cohort C) the primary endpoint will be the overall response rate of TIL treatment for patients who have not achieved PR or CR or have progressive disease from treatment of the BRAF inhibitor alone.

Study Status Information



Study Activation / Registration Date:	02/01/2006

IRB Review and Approval Date:	08/04/2004

Study Type:	Therapeutic

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients must have metastatic melanoma or stage III in-transit or regional nodal disease. (Turnstile I)

2) Patients must receive an MRI/CT of the brain or PET/CT within 6 months of consenting. If new lesions are present, PI or his designee should make final determination regarding enrollment. (Turnstile I)

3) Age greater than or equal to 12 years. (Turnstile I)

4) Clinical performance status of ECOG 0-2. (Turnstile I)

5) Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible. Patients receiving cytotoxic agents will be evaluated by the PI or his designee as to suitable eligibility. (Turnstile I)

6) Patients must be HLA-A2 for cohort A. (Turnstile II-Chemotherapy/Cell Infusion-Inclusion Criteria)

7) Patients must have adequate TIL available. (Turnstile II)

8) Patients must have measurable metastatic melanoma. (Turnstile II - Chemotherapy/Cell Infusion -Inclusion Criteria).

9) Patients may have brain lesions which measure </= 1cm each. Lesions that are >1 cm that have been treated with SRS and in the opinion of the PI or his designee no longer represents active disease will also be allowed. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).

10) Patients of both genders must practice birth control for four months after receiving the preparative regimen. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).

11) Patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery.

12) Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control. (Turnstile II)

13) Pregnancy testing will be performed within 7 days prior to treatment.

14) Clinical performance status of ECOG 0 - 2 at the time of chemotherapy infusion. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).

15) Absolute neutrophil count greater than or equal to 750/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).

16) Platelet count greater than or equal to 75,000/mm3. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).

17) Hemoglobin greater than or equal to 8.0 g/dl. (Turnstile II - Chemotherapy/Cell Infusion).

18) Serum ALT less than three times the upper limit of normal. (Turnstile II - Chemotherapy/Cell Infusion- Inclusion Criteria).

19) Serum creatinine less than or equal to 1.6 mg/dl. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).

20) Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl. (Turnstile II - Chemotherapy/Cell Infusion - Inclusion Criteria).

21) Patients in Cohort A will be randomized to receive either TIL alone or TIL plus Dendritic cells.

22) A stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiagram or other stress test that will rule out cardiac ischemia) within 6 months of lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion-Inclusion Criteria).

23) Pulmonary function tests (FEV1>65% or FVC>65%of predicted) within 6 months of lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion - Inclusion Criteria).

24) MRI/CT of the brain within 42 days of lymphodepletion. CT scan of chest/abdoment/pelvis or PET/CT within 30 days of lymphodepletion. Exception: Patients randomized to receive dendritic cells may have an MRI of the brain within 30 days of lymphodepletion. (Turnstile II-Chemotherapy/Cell Infusion-Inclusion Criteria)

25) Patients must be receiving Vemurafenib and failed to achieve PR or CR or have progressive disease in response to Vemurafenib treatment (Cohort C).

Exclusion Criteria:

1) Has had prior systemic cancer cytotoxic chemotherapy within the past four weeks at the time of the start of the lymphodepletion regimen.

2) Has had prior B-RAF or MEK targeted therapy within 7 days prior to the start of the lymphodepletion regimen (Cohort A and Cohort B).

3) Is not receiving Vemurafenib treatment (Cohort C) (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

4) Achieves PR or CR in response to Vemurafenib treatment (Cohort C).

5) Women who are pregnant or nursing will be excluded because of the potentially dangerous effects of the preparative chemotherapy on the fetus. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

6) Any active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, such as abnormal stress test and/or abnormal PFT. PI or his designee shall make the final determination regarding appropriateness of enrollment.(Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

7) Any form of primary or secondary immunodeficiency. Must have recovered immune competence after chemotherapy or radiation therapy as evidenced by lymphocyte counts (> 500/mm3), WBC (> 3,000/mm3) or absence of opportunistic infections. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

8) Require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 30 days, or have used topical or inhalational steroids in the past 2 weeks prior to lymphodepletion. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

9) Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated. (Turnstile II - Chemotherapy/Cell Infusion Exclusion Criteria)

Links

Registration Number: NCT00338377
Study Information on Clinical Trials Registry (clinicaltrials.gov)