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Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

Primary Purpose

Blasts More Than 20 Percent of Bone Marrow Nucleated Cells, Blasts More Than 20 Percent of Peripheral Blood White Cells, Myelodysplastic/Myeloproliferative Neoplasm

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Decitabine

Laboratory Biomarker Analysis

Ruxolitinib Phosphate

About this trial

This is an interventional treatment trial for Blasts More Than 20 Percent of Bone Marrow Nucleated Cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of AML (World Health Organization [WHO] classification definition of >= to 20% blasts)
In the phase I portion of the study all patients with relapsed or refractory AML are eligible; for the Phase II portion of the study, patients must have AML progressing from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20% blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea are allowed; patients with newly diagnosed or previously treated disease are eligible as long as prior therapy does not include hypomethylating agents; prior therapy for ruxolitinib for MPN is allowed
Serum biochemical values with the following limits unless considered due to leukemia:
Creatinine =< 1.5 mg/dl
Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder
Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN)
Ability to take oral medication
Ability to understand and provide signed informed consent
Performance status =< 3, unless directly related to disease process as determined by the principal investigator

Exclusion Criteria:

Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results including uncontrolled severe infections, as well as uncontrolled cardiac disease, or other organ dysfunction; patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis B and C are excluded
Nursing women, women of childbearing potential with positive blood pregnancy test within 30 days of study start, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, intrauterine device [IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of the study
Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry, excluding the placement of vascular access
Active clinically serious and uncontrolled infection

Sites / Locations

M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Treatment (ruxolitinib phosphate, decitabine) Ph1

Treatment (ruxolitinib phosphate, decitabine) Ph2

Arm Description

Patients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Patients receive 50mg ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I)

Maximum tolerated dose (MTD) is defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) is less than or equal to 17% (1 out of 6).

Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2)

Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.

Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2)

JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.

Secondary Outcome Measures

Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2)

JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood. Complete Response (CR) is defined as - The participant must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1 z 10^9/L, no need for red blood cell transfusion, platelet count>/+ 100 x 10^9/L, and normal marrow differential (</= 5 % blasts) in a normo- or hypercellular marrow. Complete Response with incomplete blood count recovery (CRi) is defined as - Same as CR but incomplete count recovery.

Full Information

NCT ID

NCT02257138

First Posted

September 26, 2014

Last Updated

June 12, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02257138

Brief Title

Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

Official Title

Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

February 12, 2015 (Actual)

Primary Completion Date

March 19, 2021 (Actual)

Study Completion Date

March 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when given together with decitabine and to see how well they work in treating patients with acute myeloid leukemia that has come back or is not responding to treatment, or has developed from a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with decitabine may be an effective treatment for acute myeloid leukemia.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the tolerability of the combination of decitabine and ruxolitinib phosphate (ruxolitinib [DI]) in patients with leukemia. (Phase I) II. To determine the efficacy of ruxolitinib in increasing and prolonging response induced by decitabine alone in patients with post myeloproliferative neoplasm acute myeloid leukemia (AML) (post MPN-AML) alternatively referred to as (myeloproliferative neoplasm - blast phase; MPN-BP). (Compared to historical response rate with decitabine alone) (Phase II) SECONDARY OBJECTIVES: I. To compare whether there is a difference in response rate patients with post-MPN AML with janus kinase 2 (JAK2) mutations and patients without JAK2 mutations. OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate followed by a phase II study. Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28 and decitabine intravenously (IV) over 1-2 hours on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Blasts More Than 20 Percent of Bone Marrow Nucleated Cells, Blasts More Than 20 Percent of Peripheral Blood White Cells, Myelodysplastic/Myeloproliferative Neoplasm, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (ruxolitinib phosphate, decitabine) Ph1

Arm Type

Experimental

Arm Description

Arm Title

Treatment (ruxolitinib phosphate, decitabine) Ph2

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Decitabine

Other Intervention Name(s)

5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib Phosphate

Other Intervention Name(s)

INCB-18424 Phosphate, Jakafi

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose of Ruxolitinib Phosphate (Phase I)

Description

Maximum tolerated dose (MTD) is defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) is less than or equal to 17% (1 out of 6).

Time Frame

Up to 6 weeks

Title

Number of Participants With a Response (Complete Response [CR] + CR With Incomplete Blood Count Recovery) (Phase 2)

Description

Time Frame

Up to 6 years

Title

Number of Participants With Post-MPN Acute Myeloid Leukemia (AML) With JAK2 Mutations (Phase 2)

Description

JAK2 mutations were assessed with the baseline Bone Marrow or Peripheral Blood.

Time Frame

Baseline

Secondary Outcome Measure Information:

Title

Number of JAK2 Positive+ and JAK2 Negative- Participants With a Response (Phase 2)

Description

Time Frame

up to 6 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of AML (World Health Organization [WHO] classification definition of >= to 20% blasts) In the phase I portion of the study all patients with relapsed or refractory AML are eligible; for the Phase II portion of the study, patients must have AML progressing from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20% blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea are allowed; patients with newly diagnosed or previously treated disease are eligible as long as prior therapy does not include hypomethylating agents; prior therapy for ruxolitinib for MPN is allowed Serum biochemical values with the following limits unless considered due to leukemia: Creatinine =< 1.5 mg/dl Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of normal (ULN) Ability to take oral medication Ability to understand and provide signed informed consent Performance status =< 3, unless directly related to disease process as determined by the principal investigator Exclusion Criteria: Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results including uncontrolled severe infections, as well as uncontrolled cardiac disease, or other organ dysfunction; patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis B and C are excluded Nursing women, women of childbearing potential with positive blood pregnancy test within 30 days of study start, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, intrauterine device [IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of the study Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry, excluding the placement of vascular access Active clinically serious and uncontrolled infection

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Farhad Ravandi-Kashani

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center Website

Learn more about this trial

Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

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