A Study of the Efficacy and Safety of Lenalidomide Combined to Escalating Doses of Chemotherapy in Intermediate-2-or High Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) With Del 5q

• Status: Unknown status
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In this trial, the investigators will test the combination of escalating doses of chemotherapy (starting at relatively low dose) with lenalidomide in intermediate-2-or high risk MDS and AML with del 5 q31. It is hoped that this combined therapy will further increase response rate in intermediate-2-or high risk MDS and AML with del 5 q31, without major toxicity in comparison to historical results obtained with chemotherapy alone in the same subset of patients.

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

Details

• Lead Sponsor: Groupe Francophone des Myelodysplasies
• Collaborator: Celgene Corporation
• Treatments: Lenalidomide; Thalidomide

Criteria

Inclusion Criteria:

1. Age ≥ 18 years

2. Must understand and voluntarily sign an informed consent form

3. Must be able to adhere to the study visit schedule and other protocol requirements

4. No contra indication to anthracycline based chemotherapy

5. Documented diagnosis of MDS, or CMML with WBC < 13,000/mm3 that meets IPSS criteria for intermediate-2 or high-risk disease, or AML with an associated del 5q[31] (the deleted chromosomal region must include 5q[31]), with or without additional cytogenetic abnormalities

6. Female subjects of childbearing potential must:

• Understand that the study medication could have a potential teratogenic risk

• Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception:

• Implant, Levonorgestrel-releasing intrauterine system (IUS) (prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection) , Medroxyprogesterone acetate depot, Tubal sterilization, Ovulation inhibitory progesterone-only pills (i.e., desogestrel), Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses.

• Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.

• Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days from the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.

• Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence

7. Male subjects must:

• Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.

• Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.

8. All subjects must:

• Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.

• Agree not to share study medication with another person and to return all unused study drug to the investigator

Exclusion Criteria:

1. Pregnant or lactating females.

2. Contra indication to anthracycline based chemotherapy.

3. Proliferative (WBC ≥ 13,000/mL) CMML.

4. Prior ≥ grade-2 NCI CTCAE (v 3.0) allergic reaction to thalidomide.

5. Prior desquamating (blistering) rash while taking thalidomide.

6. Prior history of malignancy other than MDS unless the subject has been free of disease for ≥ 5 years.

7. Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 28 days .

8. Less than 6 months since prior allogeneic bone marrow transplantation.

9. Less than 3 months since prior autologous bone marrow or stem cell transplantation.

10. Recombinant human erythropoietin (rHuEPO) therapy received within 28 days.

11. Known HIV-1 positivity.

12. Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study.

13. Creatinine Clearance< 50 ml/min

14. Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN)

15. Serum total bilirubin > 1.5 mg/dL (expect for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS).

16. Subjects with ≥ grade-2 neuropathy