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Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Antimetabolites

Enzyme Inhibitors

* Patients will receive one cycle of single agent pacritinib.
* Patients who tolerate single agent pacritinib will then receive up to 11 cycles of pacritinib and decitabine combination therapy.
* Patients who do not tolerate single agent pacritinib (require dose interruption for more than 7 days before Cycle 2 Day 1) will be considered non-evaluable and replaced.
* Pacritinib will be administered orally at a dose of 200 mg twice daily continuously for Days 1 through 28 of a 28-day cycle.
* Decitabine will be administered as a subcutaneous injection in clinic on Days 1, 5, 8, 12, 15, 19, 22, and 26 of a 28-day cycle.
* Patients may continue treatment for up to 12 cycles.

-Patients should take pacritinib at approximately the same times every day with a glass of water, with or without food.

Pacritinib

Camille Abboud, M.D.

For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose of 400 mg daily was recommended for the phase II studies.

Recently, the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy (BAT) in patients with MF was reported at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms.

Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells (HSC) without cytotoxicity and subcutaneous (SC) instead of intravenous (IV) administration may avoid high peak levels that can cause apoptosis. Furthermore, the low toxicity associated with low dose decitabine would allow for more frequent (1 to 3 times weekly) administration of the drug which would catch more cells in S-phase via greater exposure time. Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes when combined with pacritinib 400 mg daily.

Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)

A Pilot Study of Pacritinib in Combination With Low Dose Decitabine in Patients With Intermediate-High Risk Myelofibrosis or MPN/MDS Syndromes

The descriptions and grading for adverse events are found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Objective response is defined as CR (complete remission/response) + PR (partial remission/response) + CI (clinical improvement).

-Anemia response

Anemia response is only applicable for patients with baseline hemoglobin level less than 10g/dL for 8 weeks or more and requires:

\*≥2 g/dL increase in hemoglobin level

\*becoming transfusion-independent (no RBC transfusions in past 1 month)

-Platelet response

Platelet response is only applicable for patients with a baseline platelet count of less than 50 x 10\^9/L for 8 weeks or more, and requires:

* 100% increase in platelet count AND
* An absolute platelet count of at least 50 x 10\^9/L

A ≥50% reduction in the myeloproliferative neoplasm symptom assessment total symptom score

* A baseline splenomegaly that is palpable at 5-10 cm below the left costal margin becomes not palpable OR
* A baseline splenomegaly that is palpable \> 10 cm below the left costal margin decreases by ≥50% OR
* A baseline splenomegaly that is palpable \< 5 cm below the left costal margin is not eligible for spleen response OR
* MRI or CT shows ≥35% spleen volume reduction

CTI BioPharma

Washington University School of Medicine

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Leukemia, Myeloid, Accelerated Phase

Molgramostim

Sargramostim

Immunologic Factors

sargramostim

therapeutic allogeneic lymphocytes

allogeneic bone marrow transplantation

in vitro-treated bone marrow transplantation

B. Douglas Smith, MD

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. 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.

PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation followed by sargramostim in treating patients who have chronic myelogenous leukemia.

OBJECTIVES:

* Determine whether the use of sargramostim (GM-CSF) after T-cell depleted, CD34-positive cell-supplemented allogeneic bone marrow transplantation can reduce leukemic relapse in patients with chronic myelogenous leukemia.

OUTLINE: Patients receive myeloablation with busulfan and cyclophosphamide on an approved protocol. Allogeneic bone marrow is harvested and treated in vitro with anti-CD34 antibody. T-cell depleted, CD34-positive cell-supplemented bone marrow is infused on day 0. Patients receive high-dose sargramostim (GM-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover and then low-dose GM-CSF SC continuing until day 60.

Donor lymphocyte infusions or second unmodified allogeneic bone marrow transplantation without GM-CSF is considered in case of primary or secondary engraftment failure.

Patients are followed every month for 3 months, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately 6-10 years.

Sargramostim Following Allogeneic Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia

GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR (Rhu-GM-CSF) FOR REDUCTION OF LEUKEMIC RELAPSE AFTER T-LYMPHOCYTE DEPLETED ALLOGENEIC BMT FOR CHRONIC MYELOID LEUKEMIA

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)	NCT02564536	Chronic Myelomo... Juvenile Myelom... Atypical Chroni... Myeloproliferat... Myelodysplastic... Myelofibrosis	Pacritinib Decitabine	18 Years -	Washington University School of Medicine
Sargramostim Following Allogeneic Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia	NCT00002778	Leukemia	sargramostim therapeutic all... allogeneic bone... in vitro-treate...	18 Years - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)	NCT02564536	Chronic Myelomo... Juvenile Myelom... Atypical Chroni... Myeloproliferat... Myelodysplastic... Myelofibrosis	Pacritinib Decitabine	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for atypical chronic myeloid leukemia