A Phase 2 Study of GCS-100 in Combination with Chemo-immunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

• Conditions: Relapsed or refractory diffuse large B-cell lymphoma; MedDRA version: 9.1Level: LLTClassification code 10012822Term: Diffuse large B-cell lymphoma refractory

• Registration Number: EUCTR2008-004087-40-GB
• Lead Sponsor: Prospect Therapeutics, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-08
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Subject is capable of understanding the purpose and risks of the study and is able to provide written Informed Consent.

2. Subject is male or female, aged at least 18 years.

3. Subject has histologically confirmed DLBCL, bi-dimensionally measurable by CT scan, with at least 1 lesion =1.5 cm in the greatest diameter. CT scan results must be available prior to dosing to establish eligibility.

4. Subject has relapsed or relapsed/refractory disease following at least 2 cycles of R-ICE chemotherapy as salvage chemotherapy, without PR or CR.

5. Subject has =4 weeks elapsed between last chemotherapy or immunotherapy exposure.

6. Subject has Eastern Collaborative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.

7. Subject’s clinical laboratory values met all of the following criteria within the 14 days prior to Study Day 1, Cycle 1:
a) Hemoglobin =9 g/dL
b) Absolute neutrophil count >1.0 x 109/L without growth factor support. (ie, no prior myeloid colony stimulating factor use within 4 weeks prior to blood draw for screening absolute neutrophil count)
c) Platelets =75 x 109/L
d) Total bilirubin =2.0 X Institutional Upper Limit of Normal (IULN)
e) Aspartate aminotransferase/alanine aminotransferase <2.5 X IULN, or <5X IULN in subjects with liver involvement of DLBCL
f) Creatinine clearance >60 mL/min/1.73 m2
g) Serum sodium >130 mmol/L

8. Subject’s life expectancy is anticipated to be at least 3 months.

9. Female subjects of childbearing potential (ie, women who have not been surgically sterilized or have not been post-menopausal for at least 1 year) and male subjects with partners of childbearing potential must agree to use medically acceptable methods of contraception throughout the study period.

10. Subject is willing and able to comply with the prescribed treatment protocol and evaluations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject has received salvage with R-ICE in whom starting doses of any of the agents were administered at below 75% of the standard dosages defined in this study.

2. Subject has received high-dose chemotherapy with hematopoietic stem cell support or allogeneic stem cell transplantation (SCT).

3. Subject has rapidly progressive lymphoma or lymphoma threatening organ function.

4. Subjects with primary or secondary central nervous system lymphoma.

5. Subjects who have had treatment with an experimental (unlicensed) drug within 3 weeks prior to treatment with GCS 100.

6. Subject has not recovered from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy.

7. Subject has a known history of human immunodeficiency virus-related lymphoma, active hepatitis C, active hepatitis B, or prior history of infection with hepatitis B (HBcAb positive)

8. Subject has a clinically relevant active infection and/or a serious co-morbid medical condition such as recent myocardial infarction (within the last 6 months and no electrocardiographic evidence of acute ischemia or new conduction system abnormalities), unstable angina, difficult-to-control congestive heart failure, uncontrolled hypertension, difficult-to-control cardiac arrhythmias, chronic obstructive or chronic restrictive pulmonary disease, and/or cirrhosis.

9. Subject had major surgery within 4 weeks prior to Study Day 1.

10. If female, subject is pregnant or breastfeeding.

11. Subject has a concomitant disease or condition, including laboratory abnormalities, which in the opinion of the Investigator could interfere with the conduct of the study or could put the subject at unacceptable risk.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assess the efficacy of GCS-100 with rituximab, ifosfomide, mesna, carboplatin, and etoposide (R-ICE) chemotherapy in subjects with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). ;Secondary Objective: Determine the safety of GCS-100 in conjunction with cytotoxic chemotherapy.;Primary end point(s): The primary efficacy outcome is overall response, defined as the sum of the Complet Response (CR) and and Partial Response (PR) rates. Response will be determined according to the International Harmonization Project guidelines. Response rate will be calculated along with a 95% confidence interval using the method of Chang to account for the 2-stage nature of the design.