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A Clinical Study to Test the Effects of Ruxolitinib And Thalidomide Combination for Patients With Myelofibrosis

Primary Purpose

Myelofibrosis

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Thalidomide
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelofibrosis focused on measuring Ruxolitinib, Thalidomide, 16-1498

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of myelofibrosis (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk IPSS, DIPSS, DIPSS+, MIPSS70 or MIPSS70+ v2.0 score
  • Patients taking Ruxolitinib at the time of enrollment must have been taking Ruxolitinib for a minimum of 3 months, and must have been on a stable dose of Ruxolitinib for a minimum of 4 weeks immediately prior to enrollment. However, for patients in the thrombocytopenic cohort A expansion, patients taking Ruxolitinib at the time of enrollment who are deemed to have a suboptimal response or are refractory to Ruxolitinib single-agent therapy (less than partial response per IWG criteria) must have been taking Ruxolitinib for a minimum of 6 weeks, and must have been on a stable dose of Ruxolitinib for a minimum of 4 weeks immediately prior to enrollment
  • Patients taking Ruxolitinib at the time of enrollment must be deemed to have had a suboptimal response (less than partial response per IWG criteria) to Ruxolitinib single-agent therapy or deemed to have progression of disease (per IWG criteria).
  • Age ≥ 18 years at the time of signing the informed consent.
  • ECOG performance status 0 to 2.
  • Patients must have adequate organ function as demonstrated by the following:

    1. Total bilirubin ≤ 2.0 mg/dL, unless due to Gilbert's disease
    2. Serum creatinine ≤ 2.0 mg/dL.
    3. ALT and AST ≤ 3 x upper limit of normal (unless the transaminitis is considered to be related to MF, in which case ≤5 x ULN is allowed
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 14 days prior to and again within 24 hours* of starting Thalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking Thalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
  • All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of REMS®
  • Platelets ≥ 50000/uL and ANC ≥ 1000. For patients enrolled in the thrombocytopenic cohorts, platelet count must be >/= 25,000 but </= 99,000/uL.
  • All study participants must be able to swallow oral medication

Exclusion Criteria:

  • Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide, G-CSF, revlimid, clofarabine) except hydroxyurea or experimental drugs, with the exception of Ruxolitinib, less than 14 days or 5-half lives prior to starting study therapy and/or lack of recovery from all toxicity from previous therapy to grade 1 or better.
  • Known prior clinically relevant hypersensitivity reaction to Thalidomide, including the development of erythema nodosum if characterized by a desquamating rash.
  • Prior therapy with Thalidomide in combination with Ruxolitinib
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, which places the subject at unacceptable risk if he/she were to participate in the study or which confounds the ability to interpret data from the study.
  • Pregnant or lactating females.
  • Known positive for HIV or hepatitis B or C per institutional standard of care
  • Participants with prior history of thromboembolic disease (i.e. deep venous thrombosis (DVT) or pulmonary embolism (PE) within the last six months, as Thalidomide has demonstrated an increased risk of DVT or PE
  • Known to have a hypercoagulability syndrome (e.g.: antithrombin III, deficiency, anticardiolipin syndrome etc).
  • Concurrent use of any strong inducers or strong inhibitors of CYP3A4. (See Appendix F for a list of prohibited and cautionary CYP3A4 inhibitors and inducers)
  • Patients with active malignancy of other type than required for this study are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.

Sites / Locations

  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memorial Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau
  • Md Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort A: Ruxolitinib and Thalidomide

Cohort B: Ruxolitinib and Thalidomide

Arm Description

After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.

A cohort expansion, for patients with baseline thrombocytopenia, will enroll 35 additional patients After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.

Outcomes

Primary Outcome Measures

best objective response rate (ORR)
(ORR; complete response, partial response, and clinical improvement by IWG-MRT) in the first six cycles of the combination therapy. Clinical improvement for this endpoint will be defined as the change in anemia, spleen, and symptom response from the time of the initiation the combination therapy. The ORR will be defined as the best response by the completion of cycle 6 of combination therapy.

Secondary Outcome Measures

Full Information

First Posted
February 27, 2017
Last Updated
April 28, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Incyte Corporation, Celgene, M.D. Anderson Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03069326
Brief Title
A Clinical Study to Test the Effects of Ruxolitinib And Thalidomide Combination for Patients With Myelofibrosis
Official Title
Evaluation of Ruxolitinib And Thalidomide Combination as a Therapy for Patients With Myelofibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 27, 2017 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Incyte Corporation, Celgene, M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this study is to test any good and bad effects of the study drugs called ruxolitinib and thalidomide. Ruxolitinib and thalidomide could shrink the cancer, but it could also cause side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis
Keywords
Ruxolitinib, Thalidomide, 16-1498

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is a multicenter, two stage phase II trial designed to assess the effect of ruxolitinib and thalidomide combination in subjects with Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis (PMF, post-PV MF, or post-ET MF).
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: Ruxolitinib and Thalidomide
Arm Type
Experimental
Arm Description
After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.
Arm Title
Cohort B: Ruxolitinib and Thalidomide
Arm Type
Experimental
Arm Description
A cohort expansion, for patients with baseline thrombocytopenia, will enroll 35 additional patients After 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Intervention Description
Ruxolitinib will be given orally in an outpatient setting unless the patient is being seen inpatient for another reason. Ruxolitinib will be given continuously orally daily in 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Intervention Description
Thalidomide will be given orally in an outpatient setting unless the patient is being seen inpatient for another reason. thalidomide will be given continuously orally daily in 28-day cycles.
Primary Outcome Measure Information:
Title
best objective response rate (ORR)
Description
(ORR; complete response, partial response, and clinical improvement by IWG-MRT) in the first six cycles of the combination therapy. Clinical improvement for this endpoint will be defined as the change in anemia, spleen, and symptom response from the time of the initiation the combination therapy. The ORR will be defined as the best response by the completion of cycle 6 of combination therapy.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of myelofibrosis (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk IPSS, DIPSS, DIPSS+, MIPSS70 or MIPSS70+ v2.0 score Patients taking Ruxolitinib at the time of enrollment must have been taking Ruxolitinib for a minimum of 3 months, and must have been on a stable dose of Ruxolitinib for a minimum of 4 weeks immediately prior to enrollment. However, for patients in the thrombocytopenic cohort A expansion, patients taking Ruxolitinib at the time of enrollment who are deemed to have a suboptimal response or are refractory to Ruxolitinib single-agent therapy (less than partial response per IWG criteria) must have been taking Ruxolitinib for a minimum of 6 weeks, and must have been on a stable dose of Ruxolitinib for a minimum of 4 weeks immediately prior to enrollment Patients taking Ruxolitinib at the time of enrollment must be deemed to have had a suboptimal response (less than partial response per IWG criteria) to Ruxolitinib single-agent therapy or deemed to have progression of disease (per IWG criteria). Age ≥ 18 years at the time of signing the informed consent. ECOG performance status 0 to 2. Patients must have adequate organ function as demonstrated by the following: Total bilirubin ≤ 2.0 mg/dL, unless due to Gilbert's disease Serum creatinine ≤ 2.0 mg/dL. ALT and AST ≤ 3 x upper limit of normal (unless the transaminitis is considered to be related to MF, in which case ≤5 x ULN is allowed Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 14 days prior to and again within 24 hours* of starting Thalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking Thalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of REMS® Platelets ≥ 50000/uL and ANC ≥ 1000. For patients enrolled in the thrombocytopenic cohorts, platelet count must be >/= 25,000 but </= 99,000/uL. All study participants must be able to swallow oral medication Exclusion Criteria: Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide, G-CSF, revlimid, clofarabine) except hydroxyurea or experimental drugs, with the exception of Ruxolitinib, less than 14 days or 5-half lives prior to starting study therapy and/or lack of recovery from all toxicity from previous therapy to grade 1 or better. Known prior clinically relevant hypersensitivity reaction to Thalidomide, including the development of erythema nodosum if characterized by a desquamating rash. Prior therapy with Thalidomide in combination with Ruxolitinib Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, which places the subject at unacceptable risk if he/she were to participate in the study or which confounds the ability to interpret data from the study. Pregnant or lactating females. Known positive for HIV or hepatitis B or C per institutional standard of care Participants with prior history of thromboembolic disease (i.e. deep venous thrombosis (DVT) or pulmonary embolism (PE) within the last six months, as Thalidomide has demonstrated an increased risk of DVT or PE Known to have a hypercoagulability syndrome (e.g.: antithrombin III, deficiency, anticardiolipin syndrome etc). Concurrent use of any strong inducers or strong inhibitors of CYP3A4. (See Appendix F for a list of prohibited and cautionary CYP3A4 inhibitors and inducers) Patients with active malignancy of other type than required for this study are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raajit Rampal, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Facility Name
Md Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

A Clinical Study to Test the Effects of Ruxolitinib And Thalidomide Combination for Patients With Myelofibrosis

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