Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS

NCT01159028 | Completed Phase 1 DMC

• 1 other identifier: 2003-0578 (v) 08-8
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The first 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), for patients with Philadelphia Chromosome positive CML, AML, ALL and MDS. The response of the leukemia to this treatment will also be studied. The second goal of this clinical research study is to evaluate the safety and toxicity of the combination of BP1001 and concurrent low-dose ara-C (LDAC) in patients with AML.

Conditions

Recurrent Adult Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Ph1 Positive CML

Keywords

Liposomal Grb-2 treatment of CML, AML, CLL, MDS; Liposomal Grb-2 with LDAC for AML

Outcome Measures

Primary Outcomes (2)

• Safety of BP1001

  Evaluate toxicity, tolerance, and MTD of escalating doses of BP1001

  30 days

• Safety of BP1001 in combination with LDAC

  Evaluate safety and toxicity of the combination of BP1001 and concurrent LDAC using non-hematologic and hematologic measures per NCI CTCAE criteria.

  30 days

Secondary Outcomes (3)

• Optimal biologically active dose

  30 days

• In vivo pharmacokinetics

  30 days

• Correlate PK data with historical experience

  30 days

Study Arms (2)

BP1001

EXPERIMENTAL

Subjects are treated with open-label study drug (BP1001) in a dose-escalation model.

Drug: BP1001

BP1001 in combination with LDAC

EXPERIMENTAL

AML subjects are treated with open-label escalating study drug (BP1001) in combination with low dose ara-C (LDAC)

Drug: BP1001 in combination with LDAC

Interventions

BP1001 DRUG

Study drug (BP1001) is constituted in normal saline, administered by IV on twice weekly for 28 days.

Also known as: Liposomal Grb-2, L-Grb-2, BP-100-1.01

BP1001

BP1001 in combination with LDAC DRUG

Study drug (BP1001) is constituted in normal saline, administered by IV twice weekly for 28 days. Low dose ara-C (LDAC) is self administered twice daily for 10 consecutive days during the 28 day cycle.

Also known as: Liposomal Grb-2, L-Grb-2, BP-100-1.01, low dose ara-C

BP1001 in combination with LDAC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years of age or older
• A diagnosis of refractory or relapsed AML, 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:
• Blasts in Peripheral Blood or Bone Marrow ≥15%
• Promyelocytes and Blasts in Peripheral Blood or Bone Marrow ≥30%
• PB or BM basophils ≥20%
• Thrombocytopenia \<100 x 103/ml, not resulting from therapy
• Blast phase is defined as ≥30% blasts in peripheral blood or bone marrow, or presence of extramedullary disease, except for liver or spleen.
• Patients with CML must have demonstrated resistance and/or intolerance to therapy with at least 2 tyrosine kinase inhibitors (TKI)
• Patients with AML and ALL should have received at least 1 prior treatment regimen and either failed to achieve response or relapsed on treatment
• 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.
• Have clinically adequate hepatic and renal functions as defined by:
• ALT\<2x ULN
• Serum creatinine concentration \<2x ULN
• Serum bilirubin \<2x ULN

You may not qualify if:

• Serious intercurrent medical illnesses which would interfere with the ability of the patient to carry out the treatment program
• Pregnant or breastfeeding women
• Patients who have uncontrolled active infection
• Patients who have received another investigational product within the longer of 14 days or 5 half-lives of the previous product
• Any history of adverse reaction or hypersensitivity to LDAC
• 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.

Sponsors & Collaborators

• Bio-Path Holdings, Inc.: lead

Study Sites (1)

M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Ohanian M, Tari Ashizawa A, Garcia-Manero G, Pemmaraju N, Kadia T, Jabbour E, Ravandi F, Borthakur G, Andreeff M, Konopleva M, Lim M, Pierce S, O'Brien S, Alvarado Y, Verstovsek S, Wierda W, Kantarjian H, Cortes J. Liposomal Grb2 antisense oligodeoxynucleotide (BP1001) in patients with refractory or relapsed haematological malignancies: a single-centre, open-label, dose-escalation, phase 1/1b trial. Lancet Haematol. 2018 Apr;5(4):e136-e146. doi: 10.1016/S2352-3026(18)30021-8. Epub 2018 Mar 14.

  PMID: 29550383 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

• Maro Ohanian, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: July 9, 2010
• Study Start: June 1, 2010
• Primary Completion: March 30, 2017
• Study Completion: March 30, 2017
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

US (1)