Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT01028716 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 2372.00NCI-2009-014332372RG9213052
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.

Conditions

Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukaemia With Prior Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3)(Q21Q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9); Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With T(1;19)(Q23;P13.3); E2A-PBX1 (TCF3-PBX1); Ph+ ALL; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma; Hematopoietic Cell Transplant Recipient

Outcome Measures

Primary Outcomes (4)

• Non-relapse Mortality at 1 Year

  Cumulative incidence of death without evidence of disease progression at 1 year

  Up to 1 year

• Percentage of Participants With Chronic Graft Versus Host Disease

  Scored according to the National Cancer Institute criteria. Mild-to-severe chronic GVHD at 2 years.

  Up to 2 years post-transplant

• Incidence of Grades III/IV Acute Graft Versus Host Disease

  Grading determined by organ system stages. Grade III/IV acute graft versus host disease is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.

  At day 84

• Relapse of Malignancy After Transplantation

  Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.

  Up to 7 years

Secondary Outcomes (8)

• Time to Neutrophil Recovery

  Up to day 84 post-transplant

• Time to Platelet Recovery

  Up to day 84 post-transplant

• Incidence of Primary Graft Failure

  At day 84

• Disease-free Survival

  3 years from the date of transplant

• Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System

  Up to day 90

Study Arms (1)

Treatment (nonmyeloablative HCT, TBI)

EXPERIMENTAL

Patients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is \>= 1,000/mm\^3 for three consecutive days.

Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine Phosphate; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; 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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (nonmyeloablative HCT, TBI)

Filgrastim BIOLOGICAL

Given SQ

Also known as: Filgrastim XM02, Filgrastim-sndz, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim, Zarxio

Treatment (nonmyeloablative HCT, TBI)

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 (nonmyeloablative HCT, TBI)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (nonmyeloablative HCT, TBI)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo PBSC

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (nonmyeloablative HCT, TBI)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (nonmyeloablative HCT, TBI)

Tacrolimus DRUG

Given IV or PO

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

Treatment (nonmyeloablative HCT, TBI)

Total-Body Irradiation RADIATION

Undergo total-body irradiation (TBI)

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (nonmyeloablative HCT, TBI)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Molecular based human leukocyte antigen (HLA) typing will be performed for the HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity; a minimum match of 5/10 is required; an unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor
• Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as \< 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer rods) in a bone marrow with \> 20% cellularity, peripheral blood counts showing ANC \> 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp); if the marrow has \< 20% cellularity due to treatment related cytotoxicity, but still has \< 5% blasts, an exception may be made to include this patient up to principal investigator (PI) discretion
• Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following:
• Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements
• White blood cell counts \> 30,000/mcL
• Patients over 30 years of age
• Time to complete remission \> 4 weeks
• Presence of extramedullary disease
• Minimal residual disease
• Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation
• Acute myelogenous leukemia in high risk CR1 as defined by at least one of the following:
• Greater than 1 cycle of induction therapy required to achieve remission
• Preceding myelodysplastic syndrome (MDS)
• Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities
• French-American-British (FAB) M6 or M7 leukemia, or

You may not qualify if:

• HLA-matched or single allele-mismatched donor able to donate
• Pregnancy or breast-feeding
• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
• Patients with primary idiopathic myelofibrosis
• DONOR: Positive anti-donor HLA antibody

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Burkitt Lymphoma; Myelodysplastic Syndromes; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Follicular; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Multiple Myeloma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

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

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Bone Marrow Diseases; Lymphoma, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Rachel Salit
• Organization: Fred Hutchinson Cancer Center

rsalit@fredhutch.org

2066671317

Study Officials

• Rachel B. Salit

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: December 9, 2009
• Study Start: May 19, 2010
• Primary Completion: October 7, 2021
• Study Completion: October 7, 2021
• Last Updated: January 23, 2023
• Results First Posted: January 23, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)