Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis

• Status: Completed
• Trial end date: 2020-09-21
• Target enrollment: 0
• Participant gender: All

Summary

This early phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating patients with primary or secondary myelofibrosis. Drugs used in chemotherapy, such as melphalan, fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil, and filgrastim 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. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving combination chemotherapy and total body irradiation before a donor blood stem cell transplant helps to stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Lenograstim; Mechlorethamine; Melphalan; Mycophenolic Acid; Nitrogen Mustard Compounds; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

• Diagnosis of primary or secondary Myelofibrosis with transplant indication by DIPSS-plus (> intermediate -1);

• Age 18-70; patients >/= age 50 must have an comorbidity score (HCT-CI)The Principal Investigator is the final arbiter for comorbidity;

• Patients can be in chronic phase (CP) with BM blast countto AML and achieved
• Lack of an HLA matched donor or need to proceed fast to transplantation when a patient does not have an immediately available matched unrelated donor (typed by high-resolution in the registry);

• Performance status >/=70% (Karnofsky); patients > 50 years should have adequate cognitive function; any concerns regarding cognitive function should be addressed by a Geriatrician/Neurologist;

• Adequate organ function: ALT/AST/billirubin 50mls/min (calculated with Cockroft-Gault formula); LVEF >/= 50%, DLCOc >/= 50%;

• Prior treatment with JAK2 inhibitor therapy is not excluded. Patients on a JAK2 inhibitor may continue through conditioning until Day -3 then tapered at the discretion of the investigator.

Exclusion:

• Evidence of portal hypertension with varices, ascites, or hepatic encephalopathy;

->10% bone marrow blasts at transplant if no history of AML and >5% if had previous progression to AML;

• HIV positive; active hepatitis B or C;

• Patients with active infections. The PI is the final arbiter of the eligibility;

• Liver cirrhosis;

• Prior CNS involvement by tumor cells;

• Severe pulmonary hypertension (PHT) (On echo or right side cardiac catheterization);

• History of another primary malignancy that has not been in remission for at least 3 years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear);

• Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization;

• Noncompliance - Inability or unwillingness to comply with medical recommendations regarding therapy or follow-up, including smoking tobacco. Smoking cessation is a standard teaching practice prior to admission for all patients undergoing stem cell transplant. Any patient who refuses to stop smoking prior to transplant will not be eligible for this study.