Donor Umbilical Cord Blood Transplant After Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Cancer

NCT00963872 | Terminated Phase 1 Results DMC

• 4 other identifiers: 2008UC097MT2008-150809M46361RC1HL099447
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed). The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.

Conditions

Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Number of Patients With the Complement 3a (C3a) Unit Predominating

  Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.

  Day 180

Secondary Outcomes (19)

• Neutrophil Engraftment

  Day 42

• Donor Chimerism in Blood

  Day 28

• Incidence of Grades II-IV Graft-vs-host Disease

  Day 0 through Day 100

• Non-Relapse Mortality

  Day 180

• Overall Survival

  Day 360

Study Arms (2)

Complement Fragment 3A - Small Cell Dose

EXPERIMENTAL

Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.

Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: Total body irradiation; Biological: Umbilical cord blood unit with C3a fragment; Biological: Unmanipulated UCB Unit

Complement Fragment A - Larger Cell Dose

EXPERIMENTAL

Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.

Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: Total body irradiation; Biological: Umbilical cord blood unit with C3a fragment; Biological: Unmanipulated UCB Unit

Interventions

cyclophosphamide DRUG

50 mg/kg intravenously (IV) over 2 hours on Day -6.

Also known as: Cytoxan

Complement Fragment 3A - Small Cell Dose; Complement Fragment A - Larger Cell Dose

fludarabine phosphate DRUG

40 mg/m\^2 over 1 hour on Days -6 through -2.

Also known as: Fludara

Complement Fragment 3A - Small Cell Dose; Complement Fragment A - Larger Cell Dose

Total body irradiation RADIATION

200 cGy on Day -1

Complement Fragment 3A - Small Cell Dose; Complement Fragment A - Larger Cell Dose

Umbilical cord blood unit with C3a fragment BIOLOGICAL

On Day 0, the C3a primed UCB unit will be infused intravenously SECOND, within 30 minutes of the completion of the infusion of the unmanipulated UCB unit, through a central line without in-line filtration in a manner identical to the unmanipulated UCB unit.

Complement Fragment 3A - Small Cell Dose; Complement Fragment A - Larger Cell Dose

Unmanipulated UCB Unit BIOLOGICAL

On Day 0, the unmanipulated UCB unit will be infused FIRST through a central line without in-line filtration per institutional guidelines.

Complement Fragment 3A - Small Cell Dose; Complement Fragment A - Larger Cell Dose

Eligibility Criteria

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

You may qualify if:

• Disease Criteria

You may not qualify if:

• Acute myeloid leukemia: high risk CR1 (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, \> 2 cycles to obtain complete remission (CR) or erythroblastic and megakaryocytic); second or greater CR.
• Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22, t(1;19), t(4;11), other MLL rearrangements) or \> 1 cycle to obtain CR; second or greater CR.
• Burkitt's lymphoma in CR2 or subsequent CR
• Natural Killer cell malignancies
• Myeloproliferative syndromes/diseases: Chronic myelogenous leukemia (CML) in chronic or accelerated phase but patients must have failed or been intolerant to Imatinib mesylate. EXCLUDED: CML in refractory blast crisis, myelofibrosis, polycythemia vera, and essential thrombocytosis.
• Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe pancytopenia, high risk complex cytogenetics or International Prognostic Scoring System (IPSS) ≥ intermediate-2 (Int-2). Blasts must be less than 5%. If 5% or more requires therapy pre-transplant to reduce blast count to ≤5%. Patients who receive single agent 5-azacytidine, decitabine or immunomodulating drugs are eligible.
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is \< 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be \< 7.5 cm (approximately).
• Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive. Mantle-cell lymphoma that is progressive on salvage therapy is NOT eligible. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is \< 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be \< 7.5 cm (approximately).
• Umbilical Cord Blood Graft Selection - Two UCB units will be compose the graft, and each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, as well as a 4-6 antigen match to the recipient. The combined cryopreserved nucleated cell dose of the 2 units must be ≥ 3 X 10\^7/kg with each unit having a minimum cell dose of 1.5 X 10\^7/kg. UCB units will be selected according to a common umbilical cord blood graft selection algorithm
• Performance Status - adequate performance status defined as Karnofsky score ≥ 60
• Age 18 to 70 years of age; patients ≥ 70 but ≤ 75 years are eligible if the co-morbidity score is ≤ 2
• Organ Function
• Cardiac: Left ventricular ejection fraction \> 35%; absence of decompensated congestive heart failure; absence of uncontrolled arrhythmia
• Pulmonary: DLCO \> 30% of predicted; absence of O2 requirements
• Hepatic: ALT, AST, alkaline phosphatase and bilirubin \< 5 x upper limit of normal

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Minnesota Medical Center - Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Multiple Myeloma; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine phosphate; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Dr. Claudio Brunstein
• Organization: University of Minnesota

bruns072@umn.edu

612-625-3918

Study Officials

• Claudio G. Brunstein, MD, PhD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 21, 2009
• First Posted: August 24, 2009
• Study Start: March 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2013
• Last Updated: December 28, 2017
• Results First Posted: November 10, 2015

Record last verified: 2017-12

Locations

US (1)