MDACC Study Summary 2007-0259

Study Summary
No. 2007-0259:.......Lymphoma; Skin......Madeleine Duvic......Dermatology

Study Summary Title



Study Summary Number:	2007-0259

Study Title:	Protocol PDX-010: A Phase 1, Open-label Study of Pralatrexate with Vitamin B12 and Folic Acid Supplementation in Patients with Relapsed or Refractory Cutaneous T-cell Lymphoma

Physician

New Patient Referral



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

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

Phone:	713-792-4578 Contact us about clinical trials

General Information



Disease Group:	Lymphoma Skin	Supported By:	Allos Therapeutics, Inc.

Phase of Study:	Phase I	Return Visit:	1x per wk as per cohort assignment

Treatment Agents:	Pralatrexate	Home Care:	n/a

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	n/a


Description/ Intervention:	The goal of this clinical research study is to find the most effective dose and dosing schedule of PDX-010 (pralatrexate), given in combination with cyanocobalamin (Vitamin B12) and pteroylglutamic acid (folic acid) supplements, in patients with CTCL. The safety of this drug combination will also be studied.

Study Objectives / Outcomes

Primary Objectives:
To determine an effective and well-tolerated dose and schedule of pralatrexate with vitamin B₁₂and folic acid supplementation that can be administered safely to patients with relapsed or refractory cutaneous T-cell lymphoma.

Secondary Objectives:
To characterize the safety profile of pralatrexate in this group of patients (CTCL).

Study Status Information



Study Activation / Registration Date:	08/02/2007

IRB Review and Approval Date:	08/02/2007

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	56

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 with no curative treatment options available for their histologically and/or cytologically confirmed relapsed or refractory CTCL of the following subtypes:(a). Mycosis fungoides Stage IB or higher, (b). S�zary syndrome, (c). Primary cutaneous anaplastic large cell.

2) Documented progression or relapse of disease after at least 1 previous systemic therapy, defined as chemotherapy, oral bexarotene, vorinostat, interferon-a, denileukin diftitox, ECP, and anti-CD52 antibody (alemtuzumab). The patient should have clearly progressed after their last prior treatment regimen. The patient has recovered from the toxic effects of prior therapy.

3) Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2

4) Life expectancy >/= 3 months.

5) >/= 18 years of age.

6) Adequate hematological, hepatic, and renal function as defined by: absolute neutrophil count (ANC) >/= 1,500/micro/L, platelet count >/= 100,000/micro/L, (at both screening and within 3 days prior to planned dosing on cycle 1, dose 1) total bilirubin </= 1.5 mg/dL, aspartate aminotransferase (AST) and ALT </= 2.5 x ULN, creatinine </= 1.5 mg/dL or if serum creatinine is elevated then patient has a calculated creatinine clearance >/= 50 mL/min.

7) MMA serum concentration < 200 nmol/L and Hcy concentration < 10 micromol/L at screening or the patient has been on a regimen of 1 mg PO QD of folic acid for at least 10 days prior to planned start of pralatrexate and has received 1 mg IM of vitamin B12 within 10 weeks of the planned start of pralatrexate. These values may be rechecked at baseline (prior to initiation of treatment) at the investigator's discretion.

8) Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. This test is not required for patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized. Pralatrexate should not be administered to women who are breastfeeding.

9) Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate.

10) Patient has given written informed consent (IC) and privacy authorization (PA).

Exclusion Criteria:

1) Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancies other than those exceptions listed above, the patient must be disease-free for >/= 5 years. Patients with other prior malignancies less than 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease.

2) Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure Guidelines.

3) Uncontrolled hypertension (systolic > 140 mm Hg or diastolic > 90 mm Hg).

4) Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of < 100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy.

5) Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required.

6) Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.

7) Patient has had major surgery within 2 weeks of planned start of treatment.

8) Receipt of any conventional chemotherapy or radiation therapy (RT) encompassing a substantial amount of bone marrow (> 10%) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.

9) Receipt of systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.

10) Initiation of or change in dosage of topical corticosteroids within 3 weeks of study treatment (topical steroid use within 3 weeks is allowed provided the strength and use has been stable for at least 1 month; topical corticosteroids cannot be started during the study).

11) Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.

12) Receipt of a monoclonal antibody within 3 months without evidence of progression.

13) Use of oral retinoids within 4 weeks of study treatment or high-dose vitamin A (once daily multi-vitamin allowed).

14) Previous exposure to pralatrexate, unless the patient was on this study, achieved a CR or PR and was taken off study treatment because of investigator decision, and subsequently experienced disease recurrence or PD.

15) For patients who are re-entering the study only: must not have received subsequent therapy for CTCL during the time they were off the initial study treatment.

Links

Registration Number: NCT00554827
Study Information on Clinical Trials Registry (clinicaltrials.gov)