A Phase I Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1001 (L-Grb-2 Antisense Oligonucleotide) in Patients with Refractory or Relapsed Acute Myeloid Leukemia, Philadelphia Chromosome Positive Chronic Myelogenous Leukemia, or Acute Lymphoblastic Leukemia, and Myelodysplastic Syndrome
L-Grb-2 Antisense Oligonucleotide
The goal of this clinical research study is to find the highest safe dose of BP1001 , a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS), that can be given as treatment for patients with Ph+ CML, AML, ALL, or MDS. BP1001 is an antisense drug, which means it may help stop cancer cells by blocking the action of a protein that signals cancer cells to divide and increase in number. The protein that BP1001 blocks is called Grb-2. The response of the leukemia to this treatment will also be studied. In addition, the time needed for the body to process this drug will be evaluated.
Disease Group: Leukemia
Treatment Agent: L-Grb-2 Antisense Oligonucleotide
Treatment Location: Only at MDACC
Estimatated Length of Stay in Houston: No hospitalizations are expected.
Return Visit: Patients must return to clinic twice weekly.
Home Care: All treatment will be administered at M.D. Anderson Cancer Center in the ;Clinical and Translational Research Center.
To determine the toxicity and tolerance of escalating doses of BP1001. To determine the maximum tolerated dose (MTD) of BP1001. To determine the optimal biologically active dose (OBAD) of BP1001, defined as a 50% reduction in Grb-2 expression in circulating leukemia cells (flow cytometry). To determine the in vivo pharmacokinetics of BP1001. To evaluate tumor response. To assess the pharmacokinetic data to correlate to the historical experience in order to demonstrate the liposomal delivery vehicle performs as expected. To determine the safety and toxicity of the combination of BP1001 and concurrent low-dose ara-C (LDAC) in patients with AML.
IRB Review and Approval Date: 06/21/2010
Recruitment Status: Closed
Projected Accrual: N/A
1) Part A: BP1001 Dose-Escalation Cohorts:
2) Male or female patients 18 years of age or older.
3) A diagnosis of refractory or relapsed acute myeloid leukemia or Ph+ CML in chronic, accelerated, or blast phase or acute lymphoblastic leukemia, or myelodysplastic syndrome. One of the following parameters is required to meet criteria for accelerated phase CML: 1) blasts in peripheral blood or bone marrow >/=15%; 2) Promyelocytes and blasts in peripheral blood or bone marrow >/=30%; 3) PB or BM basophils >/=20%; 4) Thrombocytopenia < 100x10(3)/ml, not resulting from therapy.
4) **continued from above: Blast phase is defined as >/=30% blasts in peripheral blood or bone marrow, or presence of extramedullary disease, except for liver or spleen.
5) Pts with CML must have demonstrated resistance and/or intolerance to therapy with at least 2 tyrosine kinase inhibitors(TKI).
6) Patients with AML and ALL should have received at least one prior treatment regimen and either failed to achieve response or relapsed on treatment.
7) Patients with MDS should have failed prior therapy with a hypomethylating agent or, if associated with a 5q- chromosomal abnormality, lenalidomide. Note: Patients with 5q- unable to receive or intolerant to lenalidomide are also eligible.
8) Patients must have clinically adequate hepatic and renal functions as defined by: ALT<2x ULN; Serum creatinine concentration <2x ULN; Serum bilirubin <2x ULN.
9) Patients must sign an informed consent.
10) Women of child bearing age must have a negative serum or urine pregnancy test prior to the initiation of study drug.
11) Barrier contraceptive precautions are to be used throughout the trial by all study participants of child-bearing potential.
12) Have not received anti-cancer therapy for at least two weeks prior to study entry, with the exception of low dose ara-C (LDAC) given as subcutaneous injections (no less than 15 days prior), hydroxyurea or anagrelide (no less than 24 hours prior), TKI (no less than 5 days prior), and interferon (no less than 2 weeks prior).
13) Have an ECOG Performance of 0-2
14) Have a life-expectancy >/=3 months
15) Part B: BP1001 with Concurrent LDAC Dose-Expansion Cohorts: Enrollment in the dose-expansion cohorts (DEC) will be limited to only those patients with a diagnosis of refractory or relapsed AML (except acute promyelocytic leukemia) or those who are refractory to at least 1 prior therapy regimen and no more than 1 prior salvage regimen. Patients being considered for inclusion in the DEC must meet all other applicable eligibility criteria specified above.
1) Part A: BP1001 Dose-Escalation Cohorts:
2) Serious intercurrent medical illnesses which would interfere with the ability of the patient to carry out the treatment program.
3) Pregnant or breastfeeding women.
4) Patients who have uncontrolled active infection.
5) Patients who have received another Investigational product within the longer of 14 days or 5 half-lives of the previous product.
6) Any history of adverse reaction or hypersensitivity to LDAC.
7) Part B: BP1001 with Concurrent LDAC Dose-Expansion Cohorts: Enrollment in the dose-expansion cohorts (DEC) will be limited to only those patients with a diagnosis of refractory or relapsed AML (except acute promyelocytic leukemia) or those who are refractory to at least 1 prior therapy regimen and no more than 1 prior salvage regimen. Patients being considered for inclusion in the DEC must meet all other applicable eligibility criteria specified above.
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