Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00012376
• Date of registration: 03/03/2001
• Prospective Registration: No
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Chemotherapy Plus Sargramostim in Treating Patients With Refractory Myeloid Cancer
• Scientific title: Dose Finding Study of Bryostatin-1 and GM-CSF in Refractory Myeloid Malignancies
• Date of first enrolment: March 2001
• Target sample size: 35
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00012376
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: B. Smith
• Affiliation: Johns Hopkins University

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- Patients must have recovered from all toxicities (to grade 0 or 1) associated with
previous treatment

- Patients must not have any clinical symptoms of active CNS disease; if CNS disease is
suspected, patient must have LP with negative cytology

- Patients must not have evidence of pulmonary leukostasis (i.e., the clinical syndrome
associated with symptomatic shortness of breath or hypoxia which is directly
attributed to an elevated white blood cell count and the resulting capillary
ischemia) or disseminated intravascular coagulation (i.e., the clinical syndrome
associated with systemic intravascular clotting which is directly attributed to
excessive procoagulants that overwhelm the inhibitory arm of the coagulation cascade)

- All women of potential child bearing must have negative serum B-HCG and use an
effective means of birth control throughout the trial period

- Patients must be able to provide informed consent and to return to clinic for
adequate follow up as required by the protocol

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Untreated Adult Acute Myeloid Leukemia

Chronic Phase Chronic Myelogenous Leukemia

Recurrent Adult Acute Myeloid Leukemia

Relapsing Chronic Myelogenous Leukemia

Accelerated Phase Chronic Myelogenous Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Blastic Phase Chronic Myelogenous Leukemia

Chronic Myelomonocytic Leukemia

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Refractory Anemia

Thrombocytopenia

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Previously Treated Myelodysplastic Syndromes

Refractory Anemia With Ringed Sideroblasts

Adult Acute Myeloid Leukemia With Del(5q)

Paroxysmal Nocturnal Hemoglobinuria

Intervention(s)

Drug: bryostatin 1

Other: laboratory biomarker analysis

Biological: sargramostim

Other: pharmacological study

Primary Outcome(s)

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 [Time Frame: 56 days]

Secondary ID(s)

NCI-2012-03159

P01CA015396

J0051

Source(s) of Monetary Support

Please refer to primary and secondary sponsors