NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders

NCT00053989 | Completed Phase 2 Results DMC

• 2 other identifiers: CDR0000269673RP01-05
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops 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). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Fanconi Anemia; Aplastic Anemia

Keywords

accelerated phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; primary myelofibrosis; de novo myelodysplastic syndromes; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory anemia with excess blasts; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; Waldenstrom macroglobulinemia; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; childhood acute lymphoblastic leukemia in remission; adult acute lymphoblastic leukemia in remission; noncontiguous stage II adult lymphoblastic lymphoma; refractory multiple myeloma; refractory anemia; refractory chronic lymphocytic leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; grade 1 follicular lymphoma; grade 2 follicular lymphoma; recurrent/refractory childhood Hodgkin lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

• Day 100 TRM

  treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0

  from start or conditioning (day -6 or -5) through day +100 after HSC infusion

• Day 100 Best Response

  Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol

  from start of conditioning on day -6 or -5 through day +100 after HSC infusion

Secondary Outcomes (3)

• PFS

  1 year

• OS

  1 year

• Acute GvHD

  Day +100

Study Arms (1)

All patients

EXPERIMENTAL

All patients enrolled on study

Biological: anti-thymocyte globulin; Biological: graft-versus-tumor induction therapy; Biological: sargramostim; Biological: therapeutic allogeneic lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Procedure: umbilical cord blood transplantation

Interventions

anti-thymocyte globulin BIOLOGICAL

iv

All patients

graft-versus-tumor induction therapy BIOLOGICAL

iv

All patients

sargramostim BIOLOGICAL

iv

All patients

therapeutic allogeneic lymphocytes BIOLOGICAL

iv

All patients

cyclophosphamide DRUG

injection

All patients

fludarabine phosphate DRUG

iv

Also known as: FLUDARA

All patients

methylprednisolone DRUG

oral

All patients

mycophenolate mofetil DRUG

oral

All patients

tacrolimus DRUG

oral

All patients

allogeneic bone marrow transplantation PROCEDURE

iv

All patients

peripheral blood stem cell transplantation PROCEDURE

iv

All patients

umbilical cord blood transplantation PROCEDURE

iv

All patients

Eligibility Criteria

• Age: 4 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of aplastic anemia * Severe disease * Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin OR * Histologically confirmed hematologic malignancy including the following: * Acute leukemia * Any of the following types: * Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes * Secondary AML * AML with high-risk cytogenetic abnormalities * Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities * Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR * In first remission at high risk of relapse * Chronic myelogenous leukemia * Chronic phase meeting at least 1 of the following criteria: * Failed imatinib mesylate * Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week * Unable to tolerate interferon * Accelerated phase (blasts less than 20%) * Myeloproliferative and myelodysplastic syndromes * Myelofibrosis (after splenectomy) * Refractory anemia * Refractory anemia with excess blasts * Chronic myelomonocytic leukemia * Lymphoproliferative disease * Chronic lymphocytic leukemia * Symptomatic disease after first-line chemotherapy * Low-grade non-Hodgkin's lymphoma (recurrent or persistent) * Symptomatic disease after first-line chemotherapy * Multiple myeloma * Progressive disease after autologous stem cell transplantation * Waldenstrom's macroglobulinemia * Failed 1 standard regimen * Non-Hodgkin's lymphoma meeting the following criteria: * Intermediate or high grade * Controlled and chemosensitive disease * First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse * Hodgkin's lymphoma * Relapsed and chemosensitive disease * Not eligible for standard myeloablative allogeneic stem cell transplantation * Availability of any of the following donor types: * Related donor matched at 5 or 6 HLA antigens (A, B, DR) * Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci * Single antigen mismatch at C allowed * Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted * No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age * 4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation) * 4 to 60 (if unrelated cord blood transplantation) Performance status * Karnofsky \> 50% Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Bilirubin less than 3 times normal * Alkaline phosphatase less than 3 times normal * AST/ALT less than 3 times normal * No Child's class B or C liver failure Renal * Creatinine clearance greater than 40 mL/min Cardiovascular * Cardiac ventricular ejection fraction at least 35% by MUGA * No cardiovascular disease Pulmonary * DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV antibody negative * No uncontrolled diabetes mellitus * No active serious infection * No other disease that would preclude study therapy * No other concurrent malignancy except non-melanoma skin cancer * No concurrent serious psychiatric illness PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * patients may have received a prior autologous blood or marrow transplantation (BMT) * At least 6 months since prior allogeneic BMT Chemotherapy * See Disease Characteristics * At least 2 weeks since prior chemotherapy, radiation or surgery Endocrine therapy * Not specified Radiotherapy * At least 2 weeks since prior radiotherapy Surgery * At least 2 weeks since prior surgery

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Fanconi Anemia; Anemia, Aplastic; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myelomonocytic, Chronic; Primary Myelofibrosis; Leukemia, Myeloid, Chronic-Phase; Anemia, Refractory, with Excess of Blasts; Waldenstrom Macroglobulinemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Hodgkin Disease; Leukemia, Myeloid, Acute; Anemia, Refractory; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Recurrence; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Lymphoma, B-Cell, Marginal Zone; Congenital Abnormalities

Interventions

Antilymphocyte Serum; sargramostim; Cyclophosphamide; fludarabine phosphate; Methylprednisolone; Mycophenolic Acid; Tacrolimus; Peripheral Blood Stem Cell Transplantation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Anemia, Hypoplastic, Congenital; Anemia; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Leukemia, B-Cell

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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Theresa Hahn, PhD
• Organization: Roswell Park Comprehensive Cancer Center

theresa.hahn@roswellpark.org

716084505819

Study Officials

• Philip L. McCarthy, MD

  Roswell Park Cancer Institute

  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: SPONSOR

Study Record Dates

• First Submitted: February 5, 2003
• First Posted: February 6, 2003
• Study Start: January 29, 2002
• Primary Completion: July 19, 2018
• Study Completion: July 19, 2018
• Last Updated: February 10, 2020
• Results First Posted: February 10, 2020

Record last verified: 2019-12

Locations

US (1)