Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy

NCT00303719 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2001LS058UMN-MT2001-100108M06725
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.

Conditions

Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma; Plasma Cell Neoplasm; Myelodysplastic Syndromes

Keywords

leukemia; lymphoma; myeloma

Outcome Measures

Primary Outcomes (1)

• Neutrophil and Donor Cell Engraftment

  Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin \> 0.5 x 10e9 /L for 3 days by day 42

  Day 42 and Day 100

Secondary Outcomes (4)

• Serious Adverse Events

  Day 100

• Transplant Related Mortality

  Day 100

• Overall Survival

  1 year

• Acute Graft-Versus-Host Disease

  Day 100

Study Arms (2)

High Risk Patients

EXPERIMENTAL

Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.

Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: stem cell transplantation; Radiation: total body irradiation; Drug: filgrastim

Standard Risk Patients

EXPERIMENTAL

Nonmyeloablative conditioning using fludarabine, cyclophosphamide and low dose Total Body Irradiation with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation, immunosuppressive cyclosporine and mycophenolate mofetil and post-transplant use of bone marrow-stimulating filgrastim.

Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine; Drug: mycophenolate mofetil; Procedure: stem cell transplantation; Radiation: total body irradiation; Drug: filgrastim

Interventions

anti-thymocyte globulin BIOLOGICAL

ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4. Those that should/will receive ATG in the preparative regimen: * Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should * Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will * Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should * Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.

Also known as: ATG

High Risk Patients; Standard Risk Patients

cyclophosphamide DRUG

Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.

Also known as: Cytoxan

High Risk Patients; Standard Risk Patients

cyclosporine DRUG

Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of \>200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.

Also known as: CSA

High Risk Patients; Standard Risk Patients

fludarabine DRUG

Fludarabine 30 mg/m\^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m\^2 for 5 days.

Also known as: Fludara

High Risk Patients; Standard Risk Patients

mycophenolate mofetil DRUG

Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if \< 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) \> 0.5 x 109 /L).

Also known as: MMF

High Risk Patients; Standard Risk Patients

stem cell transplantation PROCEDURE

On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.

Also known as: peripheral blood stem cell transplantation, bone marrow transplant

High Risk Patients; Standard Risk Patients

total body irradiation RADIATION

The dose of TBI will be 200 cGy given in a single fraction on day -1.

Also known as: TBI

High Risk Patients; Standard Risk Patients

filgrastim DRUG

Patients with white blood cell (WBC) counts \< 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) \> 2500 for 2 consecutive days.

Also known as: G-CSF

High Risk Patients; Standard Risk Patients

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with aplasia) will be considered separately in Arm 7.
• Age and Graft criteria (all patients)
• Patient's \< or = 75 years old with a 5/6 or 6/6 related donor match are eligible.
• Patient's \< or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match are eligible.
• Disease Criteria (standard risk patients)
• Acute myelogenous leukemia
• Acute lymphocytic leukemia
• Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible).
• Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple myeloma demonstrating chemosensitive disease
• Acquired bone marrow failure syndromes
• Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all IPSS categories if severe pancytopenia, transfusion requirements not responsive to therapy, or high risk cytogenetics. Blasts must be less than 5%. If \>5% requires therapy (induction or Hypomethylating agents) pre-transplant to decrease disease burden.
• Renal cell cancer,
• Chronic myeloproliferative disorder, i.e. myelofibrosis
• Disease Criteria (High risk patients on Arm 7)
• Patients with refractory leukemia or MDS may be taken to transplant in aplasia after induction or re-induction chemotherapy or radiolabeled antibody. These high risk patients will be analyzed separately in Arm 7.

You may not qualify if:

• Pregnancy or breast feeding
• Evidence of HIV infection or known HIV positive serology
• Active serious infection
• Congenital bone marrow failure syndrome
• Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI)
• Chronic myelogenous leukemia (CML) in refractory blast crisis
• Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
• Multiple Myeloma progressive on salvage chemotherapy.
• DONOR ELIGIBILITY
• Related will undergo apheresis - if donor is unable to undergo apheresis, a bone marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone marrow harvest or apheresis.
• All donors must be able to give informed consent.
• Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for suitability of the apheresis procedure. Informed consent must be obtained from parent or guardian as applicable for minors.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (5)

• Warlick E, Ahn KW, Pedersen TL, Artz A, de Lima M, Pulsipher M, Akpek G, Aljurf M, Cahn JY, Cairo M, Chen YB, Cooper B, Deol A, Giralt S, Gupta V, Khoury HJ, Kohrt H, Lazarus HM, Lewis I, Olsson R, Pidala J, Savani BN, Seftel M, Socie G, Tallman M, Ustun C, Vij R, Vindelov L, Weisdorf D. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era. Blood. 2012 Apr 26;119(17):4083-90. doi: 10.1182/blood-2012-02-409763. Epub 2012 Mar 9.

  PMID: 22408257 BACKGROUND

• Warlick ED, DeFor TE, Bejanyan N, Holtan S, MacMillan M, Blazar BR, Dusenbery K, Arora M, Bachanova V, Cooley S, Lazaryan A, McGlave P, Miller JS, Rashidi A, Slungaard A, Vercellotti G, Ustun C, Brunsein C, Weisdorf D. Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up. Biol Blood Marrow Transplant. 2019 Jan;25(1):56-62. doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.

  PMID: 30077015 BACKGROUND

• Bachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.

  PMID: 22430088 DERIVED

• Bachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.

  PMID: 21403127 DERIVED

• Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.

  PMID: 19179301 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Kidney Neoplasms; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes

Interventions

Antilymphocyte Serum; Cyclophosphamide; Cyclosporine; fludarabine; fludarabine phosphate; Mycophenolic Acid; Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Bone Marrow Transplantation; Whole-Body Irradiation; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Tissue Transplantation; Radiotherapy; Investigative Techniques; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Results Point of Contact

• Title: Erica Warlick, MD
• Organization: Masonic Cancer Center, University of Minnesota

ewarlick@umn.edu

612-625-8942

Study Officials

• Erica Warlick, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 17, 2006
• Study Start: March 26, 2002
• Primary Completion: May 8, 2019
• Study Completion: May 8, 2019
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-04

Locations

US (1)