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

NCT03426969 | Completed Early Phase 1 FDA Drug

• 3 other identifiers: 2017-0375NCI-2018-00910P30CA016672
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Observed toxicities will be tabulated and 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 day +100 post-hematopoietic cell transplantation (HCT)

Secondary Outcomes (8)

• Overall survival

  Up to 24 months

• Progression-free survival

  Up to 24 months

• Graft failure-free survival

  Up to 24 months

• Time to neutrophil recovery

  Up to 24 months

• Time to platelet recovery

  Up to 24 months

Study Arms (1)

Treatment (combination chemotherapy, TBI, HCT)

EXPERIMENTAL

Patients receive melphalan IV over 30 minutes on days -5, fludarabine phosphate IV over 1 hour on days -5 to -2. Patients undergo TBI on day -1 and HCT on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously for approximately 2 weeks, then PO for 6 months followed by a taper, mycophenolate mofetil PO TID until day 100, and filgrastim SC daily from day 7 until continued until ANC \> 1,500/mm\^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.

Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Radiation: Total-Body Irradiation

Interventions

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)

Filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (combination chemotherapy, TBI, HCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (combination chemotherapy, TBI, HCT)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HCT

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

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

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 - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) \</= 4 (Sorror). The Principal Investigator is the final arbiter for comorbidity;
• Patients can be in chronic phase (CP) with BM blast count \</= 10% or after progression to AML and achieved \</= 5% BM blasts (morphologic CR prior to transplant);
• 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 \</= 5X UNL, creatinine clearance \> 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine phosphate; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Melphalan; Mycophenolic Acid; Tacrolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Study Officials

• Stefan O Ciurea

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 8, 2018
• Study Start: January 31, 2018
• Primary Completion: September 21, 2020
• Study Completion: September 21, 2020
• Last Updated: October 14, 2020

Record last verified: 2020-10

Locations

US (1)