Ruxolitinib Phosphate, Tacrolimus and Sirolimus in Preventing Acute Graft-versus-Host Disease During Reduced Intensity Donor Hematopoietic Cell Transplant in Patients With Myelofibrosis

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with tacrolimus and sirolimus in preventing acute graft-versus-host disease during reduced intensity donor hematopoietic cell transplant in patients with myelofibrosis. Sometimes transplanted cells from a donor can attack the normal tissue of the transplant patient called graft-versus-host disease. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It may also reduce graft-versus-host disease by reducing inflammation and immune modulation. Giving ruxolitinib phosphate together with tacrolimus and sirolimus after transplant may prevent graft-versus-host disease.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Everolimus; Fludarabine; Fludarabine phosphate; Mechlorethamine; Melphalan; Nitrogen Mustard Compounds; Sirolimus; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

• Primary or secondary myelofibrosis intermediate or high risk by Dynamic International Prognostic Scoring System 26 (DIPSS26) in chronic or accelerated phase

• Transformed acute myeloid leukemia (AML) with marrow fibrosis is allowed, if AML is in complete remission after induction therapy

• Patients with a performance status of >= 70% on the Karnofsky scale

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 1 year following transplant as per City of Hope standard operating procedure, (SOP) for allogeneic transplantation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

• Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as JAK-2, myeloproliferative leukemia [MPL] and calreticulin [CALR] mutational status) will be obtained as per standard practice

• Bone marrow aspirates/biopsies should be performed within 23 ± 7 days from registration to confirm disease remission status

• All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate bone marrow or primed blood stem cells or an 8/8 allele-matched unrelated donor

• All ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)

• A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of 50% established by multi gated acquisition scan (MUGA) or echocardiogram

• Patients must have creatinine of less than or equal to 1.5 mg/dL or creatinine clearance > 60 ml/min

• A bilirubin of up to 2.0 mg/dL, excluding patients with Gilbert's disease

• Patients should also have a serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal

• Pulmonary function test including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV1) and DLCO should be greater than 50% of predicted normal value

• All subjects must have the ability to understand and the willingness to sign a written informed consent that has been approved by the City of Hope (COH) Institutional Review Board (IRB); the patient, a family member and transplant staff physician (physician, nurse, and social worker) will meet at least once prior to the subject signing consent; during this meeting all pertinent information with respect to risks and benefits to donor and recipient will be presented; alternative treatment modalities will be discussed; the risks are explained in detail in the enclosed consent form

• Prior therapy with hydroxyurea, interferon, anagrelide, ruxolitinib, hypomethylating agents, Revlimid, thalidomide, steroids, other JAK inhibitors is allowed for AML patients who are back in chronic phase MPN, prior induction chemotherapy is allowed

• DONOR: Donor evaluation and eligibility will be assessed as per current City of Hope SOP

Exclusion Criteria:

• Patients should not have any uncontrolled illness including ongoing or active infection

• Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib

• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ruxolitinib

• Patients with active 2nd malignancies other than myelofibrosis, AML, excised skin cancer, early stage cervical and prostate cancer

• Previous allogeneic hematopoietic stem cell transplantation

• Any psychiatric, social or compliance issues that, in the treating physician opinion, will interfere with completion of the transplant treatment and follow up

• Patients who have been treated with chemotherapy or radiation within two weeks of planned study enrollment; this does not include hydroxyurea or ruxolitinib, which may be continued until start of conditioning therapy

• Non-compliance defined as any subject, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study