Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active over 18 Pharmaceutical / Industry APL-B-014-03 NCT00229203

Trial Description

Summary

This is a phase IIa study to test the safety and efficacy of a new investigational compound in patients affected with multiple myeloma that have received previous chemotherapy. Subjects who meet all the entry criteria should sign a informed consent form before entering the study. Participants will be required to attend regular clinic visits to receive the study medication and have their status monitored. The clinical investigator will provide the patients with detailed explanations about this study.

Eligibility Criteria

Inclusion criteria

1. Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient’s legal representative if in accordance with local laws and regulations

2. Age > 18 years

3. Performance status (ECOG) < 2

4. Life expectancy > 3 months..

5. Patient was previously diagnosed with MM based on standard criteria (Appendix 2) and currently requires treatment because MM relapses following a response to standard chemotherapy or high-dose chemotherapy, or MM is refractory (i.e., failure to achieve at least CR, PR, or SD) to their most recent chemotherapy.

6. Patient has measurable disease, defined as follows:

1. For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.

2. For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan).

7. Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 sensitive peripheral neuropathy is allowed.

8. Patient has the following laboratory values within 14 days before day1, cycle 1:

1. Platelet count ≥ 50 x109/L, hemoglobin ≥ 8.0 g/dl and absolute neutrophil count (ANC) ≥ 1.0x109/L; lower values may be accepted if clearly are due to bone marrow involvement by multiple myeloma.

2. Corrected serum calcium < 14mg/dL.

3. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.

4. Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.

5. Total bilirrubin: ≤ 1.5 x the upper limit of normal.

6. Calculated Creatinine clearance: ≥ 40 mL/minute (by means of Crockoft and Gault´s formula, see Appendix 3 of the protocol).

9. Left ventricular ejection fraction within normal limits.

Exclusion criteria

1. Prior therapy with Aplidin®.

2. Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)

3. History of another neoplastic disease. The exceptions are:

1. non-melanoma skin cancer,

2. carcinoma in situ of uterine cervix,

3. any other cancer curatively treated and no evidence of disease for at least 10 years.

4. Other relevant diseases or adverse clinical conditions:

1. History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.

2. Previous mediastinal radiotherapy.

3. Uncontrolled arterial hypertension despite optimal medical therapy.

4. Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².

5. Symptomatic arrhythmia or any arrhythmia requiring treatment.

6. Abnormal ECG (see Appendix 5).

7. History of significant neurological or psychiatric disorders

8. Active infection

9. Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.

10. Myopathy or any clinical situation that causes significant and persistent elevation of CK (>2.5 ULN in two different determinations performed with one week appart)

11. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)

12. Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)

5. Limitation of the patient’s ability to comply with the treatment or follow-up protocol.

6. Treatment with any investigational product in the 30 days period before inclusion in the study or radiotherapy in the 4 weeks before inclusion in the study. Other previous treatments should have been completed 3 weeks before inclusion in the study, and in case of high dose chemotherapy, 8 weeks.

7. Known hypersensitivity to Aplidin®, mannitol, cremophor, or ethanol or dexamethasone.

Trial Contact Information

Trial Lead Organizations/Sponsors

PharmaMar USA

Paul Gerard Guy Richardson

Study Chair

Cesar Pico, MD		Ph: +34 91 823 4513
		Email: cpico@pharmamar.com

U.S.A.
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Paul Richardson, MD	Ph: 617-632-2104
			Email: paul_richardson@dfci.harvard.edu
		Paul Gerard Guy Richardson	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00229203
Information obtained from ClinicalTrials.gov on May 27, 2008