Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer

NCT00012376 | Completed Phase 1

• 3 other identifiers: NCI-2012-03159J0051P01CA015396
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Phase I trial to study the effectiveness of bryostatin 1 combined with sargramostim in treating patients who have refractory myeloid cancer

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Relapsing Chronic Myelogenous Leukemia; Thrombocytopenia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• MTD defined as the dose at which the CRM estimates that 30% of patients will experience dose-limiting toxicity (DLT) assessed using CTC version 2.0

  56 days

Study Arms (1)

Treatment (bryostatin 1 and sargramostim)

EXPERIMENTAL

Patients receive bryostatin 1 IV continuously and GM-CSF subcutaneously once daily on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with disease stabilization or improvement may continue treatment for up to 12 courses.

Drug: bryostatin 1; Biological: sargramostim; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

bryostatin 1 DRUG

Given IV

Also known as: B705008K112, BRYO, Bryostatin

Treatment (bryostatin 1 and sargramostim)

sargramostim BIOLOGICAL

Given subcutaneously

Also known as: GM-CSF, Leukine, Prokine

Treatment (bryostatin 1 and sargramostim)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (bryostatin 1 and sargramostim)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (bryostatin 1 and sargramostim)

Eligibility Criteria

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

You may qualify if:

• The diagnosis of MDS must be confirmed by a bone marrow aspirate and/or biopsy revealing refractory anemia, or primary refractory leukopenia or thrombocytopenia with morphologic features of MDS; patients with 5q- syndrome are ineligible; patients with RA and RARS are eligible provided they are transfusion dependent. Patients with chronic myelomonocytic leukemia (CMMoL) are eligible; allogeneic BMT will be the treatment priority for patients with HLA-matched siblings; MDS patients for whom intensive chemotherapy has failed to achieve remission will be candidates for this trial if the chemotherapy was administered \> 1 month prior to enrollment, and performance status is adequate; patients are also eligible having previously progressed on other institutional trials, including phenylbutyrate and ATRA or 5'-azacytadine
• Patients must have a bone marrow aspirate or biopsy confirmed diagnosis of relapsed AML within 4 weeks of registering for this trial; patients will be eligible only if their WBC is \< 30 x 103/:l and stable for at least 7 days, and if they are unlikely to require cytotoxic therapy during the duration of the trial; patients may not have APL
• Newly diagnosed patients may be considered for this trial provided they do not qualify for potentially curative intensive chemotherapeutic regimens; patients with APL are not eligible for this trial; patients who have refused chemotherapy for untreated AML, or who are deemed to be poor candidates medically for AML induction chemotherapy, but otherwise meet the criteria list below may enroll on this trial
• Patients with accelerated or myeloid blast phase CML are eligible if their blast count is \< 30 x 103/:L and stable for at least 7 days; patients previously treated for chronic phase CML will be eligible for this protocol; patients may also have undergone treatment for acceleration or blastic phase provided this is not within 2 weeks of enrollment and they meet all the eligibility criteria
• All patients with PNH will be eligible provided they are experiencing symptoms associated with their disease; in particular, patients experiencing life-threatening complications of their illness, including abdominal, central vein or cerebral thromboses, active infections, as well as recurrent, symptomatic hemolytic crises and do not have other treatment options are encouraged to consider participation
• JHOC confirmed and documented diagnosis of either AML, MDS, CML in accelerated or blast phase or PNH
• Patients must have relatively stable bone marrow function for more than ten days prior to enrollment on the study; WBC count doubling within this time period would indicate unstable bone marrow function
• ECOG performance status of 0, 1, 2
• Patients must have central intravenous access; acceptable access include: PICC lines, hickman and hohn catheters, and port-a-caths
• Patient or caregiver must be willing to perform subcutaneous injection
• Serum creatinine \< 2.0 mg/dL
• Total serum bilirubin =\< 1.6 mg/dL, unless secondary to hemolysis
• SGOT/SGPT each \< 2 times the upper limit of normal unless disease related (i.e., PNH, extramedullary disease)
• Hemoglobin should be at least 8 gm/dL at the time of protocol entry; patients may receive transfusions to achieve this level
• Patients must not have received treatment for their myeloid disorder within 2 weeks of beginning the trial; treatments include the use of chemotherapy, hematopoietic growth factors, and biologic therapy such as monoclonal antibodies; the exception is the use of hydroxyurea for patients with WBC \> 10 x 103/:L; this duration of time appears adequate for wash out due to the relatively short-acting nature of most anti-leukemia agents

You may not qualify if:

• Diagnosis of RA with 5q- syndrome
• Leukemia with blast count \> 30 x 103/:L, uncontrolled with hydroxyurea
• APL
• CML in lymphoid blast phase
• ECOG performance status \>= 3
• Patients with untreated positive blood cultures or radiographic evidence of active infections
• Patients with active CNS disease
• Patients with a previous history of intolerance to GM-CSF
• Pregnant or lactating women are not eligible for this protocol; all patients with child-bearing potential must use effective contraception
• Patients who have received bryostatin-1 in the past are not eligible for this protocol

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Blast Crisis; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Hemoglobinuria, Paroxysmal; Leukemia, Myeloid, Acute; Anemia, Refractory; Thrombocytopenia

Interventions

bryostatin 1; Bryostatins; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myelodysplastic-Myeloproliferative Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Polyether Toxins; Polyether Polyketides; Ethers, Cyclic; Ethers; Organic Chemicals; Macrolides; Polyketides; Lactones; Macrocyclic Compounds; Polycyclic Compounds; Marine Toxins; Toxins, Biological; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins

Study Officials

• B. Smith

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 3, 2001
• First Posted: January 27, 2003
• Study Start: March 1, 2001
• Primary Completion: January 1, 2010
• Last Updated: January 9, 2013

Record last verified: 2013-01

Locations

US (1)