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

NCT03118492 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 16420NCI-2017-00613P30CA033572
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating patients with secondary myelofibrosis. Drugs used in chemotherapy 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.

Conditions

Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  Assessed by Bearman Toxicity Scale and National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (CTCAE) 4.03. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study regimen and reversibility or outcome.

  Up to 100 days post-hematopoietic cell transplantation (HCT)

• Incidence of unacceptable toxicity

  Assessed by Bearman Toxicity Scale and NCI CTCAE version 4.03. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study regimen and reversibility or outcome.

  Up to 2 years

Secondary Outcomes (10)

• Neutrophil recovery

  Up to 2 years

• Platelet recovery

  Up to 2 years

• Incidence of cytokine release syndrome (CRS)

  After haploidentical HCT, assessed up to 2 years

• Graft failure-free survival

  Time from start of protocol treatment/infusion of stem cell product to graft-failure, death (from any cause), or last contact, whichever occurs first, assessed up to 2 years

• Overall survival

  Time from start of protocol treatment/infusion of stem cell product to death (from any cause), or last contact, whichever occurs first, assessed up to 36 months

Study Arms (1)

Treatment (combination chemotherapy, TBI, HCT)

EXPERIMENTAL

Patients receive melphalan IV over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo TBI on day -1 and HCT on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then PO for 6 months followed by a taper, mycophenolate mofetil PO TID until day 35, and G-CSF IV daily until absolute neutrophil count \> 1,500/mm\^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Glycosylated Recombinant Human G-CSF AVI-014; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo HCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (combination chemotherapy, TBI, HCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (combination chemotherapy, TBI, HCT)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (combination chemotherapy, TBI, HCT)

Glycosylated Recombinant Human G-CSF AVI-014 BIOLOGICAL

Given IV

Also known as: AVI-014

Treatment (combination chemotherapy, TBI, HCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (combination chemotherapy, TBI, HCT)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (combination chemotherapy, TBI, HCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: CellCept, MMF

Treatment (combination chemotherapy, TBI, HCT)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (combination chemotherapy, TBI, HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Treatment (combination chemotherapy, TBI, HCT)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of primary of secondary myelofibrosis with transplant indication by Dynamic International Prognostic Scoring System (DIPSS)-plus (\> intermediate-1)
• Patients \>= age 50 must have a comorbidity score (hematopoietic cell transplant-comorbidity index \[HCT-CI\]) \< 4 (Sorror)
• Patients can be in chronic phase (CP) with bone marrow (BM) blast count =\< 15% as long as no evidence of disease acceleration per principal investigator (PI) and treating physician's opinion or after progression to acute myeloid leukemia (AML) and achieved =\< 5% BM blasts (morphologic complete remission \[CR\] prior to transplant)
• Lack of an human leukocyte antigen (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
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin =\< 5 X upper limit of normal (ULN)
• Measured creatinine clearance \> 60 mls/min
• Left ventricular ejection fraction (LVEF) \>= 50%
• Corrected carbon monoxide diffusing capability (DLCOc) \>= 50%
• No active infections
• Prior treatment with JAK2 inhibitor therapy is not excluded; a JAK2 inhibitor will need to be stopped 1-2 days prior to starting conditioning regimen
• DONOR: Documented informed consent per local, state and federal guidelines
• DONOR: Genotypically haploidentical as determined by HLA typing
• Preferably a non-maternal HLA haploidentical relative due to data of high incidence of graft failure with use of maternal HLA haploidentical cells
• Eligible donors include biological parents, siblings or half-siblings, children, or cousins in rare instances

You may not qualify if:

• Evidence of severe portal hypertension with evidence of decompensation either with bleeding varices, large volume ascites, or hepatic encephalopathy
• In a bone marrow biopsy 4 weeks prior to start of conditioning on study:
• \> 15% bone marrow blasts at transplant if no history of AML and per PI and treating physician's opinion of disease acceleration
• \> 5% if had previous progression to AML
• Human immunodeficiency virus (HIV) positive; active hepatitis B or C
• Patients with active infections; the PI is the final arbiter of the eligibility
• Patients with evidence of severe pulmonary hypertension by echocardiogram and confirmed by a subsequent right side cardiac catheterization pre-enrollment
• Liver cirrhosis
• Prior central nervous system (CNS) involvement by tumor cells
• 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 papanicolaou \[PAP\] smear)
• Positive beta human chorionic gonadotropin (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
• DONOR: Has undergone solid organ, stem cell, bone marrow or blood transplantation
• DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy
• DONOR: Active infection

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Interventions

Stem Cell Transplantation; Cyclophosphamide; fludarabine; Melphalan; Mycophenolic Acid; Tacrolimus; Whole-Body Irradiation

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Study Officials

• Monzr M Al Malki

  City of Hope Medical Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 18, 2017
• Study Start: May 24, 2017
• Primary Completion (Estimated): May 26, 2026
• Study Completion (Estimated): May 26, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

US (1)