Reduced-Intensity Regimen Before Donor Bone Marrow Transplant in Treating Patients With Myelodysplastic Syndromes

NCT00045305 | Completed Phase 2 Results

• 3 other identifiers: CDR0000256928E1902U10CA021115
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Photopheresis treats the patient's blood with drugs and ultraviolet light outside the body and kills the white blood cells. Giving photopheresis, pentostatin, and radiation therapy before a donor bone marrow or stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before transplant and cyclosporine or mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving pentostatin together with photopheresis and total-body irradiation work before donor bone marrow transplant in treating patients with myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  Completed response is defined as: Bone marrow evaluation: Repeat bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia (see dysplasia qualifier under peripheral blood evaluation). Peripheral blood evaluation \[absolute values must last at least 2 months\] Hemoglobin \>11 g/dl (untransfused, not on erythropoietin) Neutrophils (1500/mm3 (not on a myeloid growth factor)) Platelets (100,000/mm3 (not on a thrombopoetic agent)) Blasts - 0% No dysplasia. No detectable cytogenetic abnormality, if preexisting abnormality was present

  Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

Secondary Outcomes (5)

• Number of Patients Who Developed Disease Progression After Achieving Complete Response

  Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

• Overall Survival

  Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

• Proportion of Graft Versus Host Disease

  Monthly for the first 3 months from study entry, every 3 months for the first two years from study entry thereafter and then every 6 months for years 3-5.

• Time to Engraftment for Neutrophil

  Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

• Time to Engraftment for Platelet

  Daily while hospitalized and then at least 1x/week for the first 50 days and then at least every other week until day 100.

Study Arms (1)

Arm I

EXPERIMENTAL

Preparative Regimen: Patients underwent photopheresis on two consecutive days and received pentostatin 4 mg/m2/d (total dose = 8 mg/m2) by continuous IV infusion on two consecutive days following photopheresis. Total body irradiation was administered on two consecutive days following pentostatin for a total of 600 cGy given in three 200 cGy fractionated doses. Transplantation: Unmanipulated allogeneic bone marrow or G-CSF mobilized peripheral blood stem cells were infused on day 0 within 48 hours of completion of TBI. Minimum cell dose was 2 ×106 CD34 cells/kg recipient. Acute graft-vs-host-disease (GVHD) prophylaxis: Patients received Cyclosporine or Tacrolimus per institutional preference or protocol beginning no later than day -1. Methotrexate (MTX) was administered on day +1 and +3. Mycofenolate mofetil (MMF) was introduced on day 100 and could be tapered and discontinued after 12 months if no active cGVHD.

Drug: Cyclosporine; Drug: Methotrexate; Drug: Photopheresis; Drug: Mycofenolate mofetil; Drug: Pentostatin; Procedure: allogeneic bone marrow; Procedure: peripheral blood stem cell; Radiation: Total body irradiation

Interventions

Cyclosporine DRUG

Immunosuppressant

Also known as: Sandimmune®, cyclosporin A, Neoral®Gengraf®, Gengraf®, CSA

Arm I

Methotrexate DRUG

Antimetabolite

Also known as: Methotrexate sodium, MTX, Mexate, Mexate-AQ, Folex, Folex PFS, Abitrexate, Rheumatrex, Amethopterin

Arm I

Photopheresis DRUG

Psoralens

Also known as: 8-methoxypsoralen, Uvadex ®, Methoxsalen

Arm I

Mycofenolate mofetil DRUG

an antibiotic with immunosuppressamt properties isolated from Penicillium spp

Also known as: Cellcept®, RS-61443, mycophenolic acid, Lilly-68618, MMF, Mycophenolate mofetil

Arm I

Pentostatin DRUG

Purine analogue

Also known as: DCF, 2-Deoxycoformycin, Nipent

Arm I

allogeneic bone marrow PROCEDURE

Unmanipulated allogeneic bone marrow

Arm I

peripheral blood stem cell PROCEDURE

G-CSF mobilized peripheral blood stem cell

Arm I

Total body irradiation RADIATION

a total of 600 cGy given in 3 200 cGy fractionated doses

Also known as: radiation therapy

Arm I

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of the following cytologically proven myelodysplastic syndromes
• Refractory anemia (RA)
• RA with ringed sideroblasts
• RA with excess blasts
• Chronic myelomonocytic leukemia
• International Prognosis Scoring System (IPSS) score of at least 0.5 OR red cell transfusion dependence for at least 6 months (2 units per month)
• Patients with an IPSS score less than 0.5 may be eligible provided they previously had a higher IPSS score and received chemotherapy at that time
• Suitable human leukocyte antigen (HLA)-matched donor (related or unrelated) available
• No cord blood donors
• Related donors must be genotypically matched (HLA A, B and DR) at 5/6 or 6/6 loci and may be a sibling, parent, or child
• Unrelated donors must have high resolution typing done at A, B, C and DR, and must be matched at all or may have a single antigen or allele mismatch at no more than one of these loci
• Patients must have \< 20% blasts on bone marrow study within 1 month of study entry
• Age of 18 to 70 years
• Eastern Cooperative Oncology Group performance status 0-1
• Life expectancy at least 6 months

You may not qualify if:

• Pregnant or nursing
• Having other medical condition that would reduce life expectancy
• Active ongoing infection
• Prior myeloablative or nonmyeloablative allogeneic transplantation for Myelodysplastic syndrome or acute myeloid leukemia

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Tufts-NEMC Cancer Center

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Jewish Hospital Cancer Center

Cincinnati, Ohio, 45236, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders

Interventions

Cyclosporine; Cyclosporins; Methotrexate; merphos; Photopheresis; Methoxsalen; Mycophenolic Acid; Pentostatin; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 3-Ring; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Investigative Techniques

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

617-632-3012

Study Officials

• Selina M. Luger, MD

  Abramson Cancer Center at Penn Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2002
• First Posted: January 27, 2003
• Study Start: October 24, 2006
• Primary Completion: February 1, 2014
• Study Completion: September 1, 2014
• Last Updated: June 28, 2023
• Results First Posted: January 19, 2015

Record last verified: 2023-06

Locations

US (6)